#MDR1 Gene Mutation

[drjeandoddspethealthresource]

MDR1 Gene Mutation in Dogs and Cats

The MDR1 Gene Mutation is fairly easy to understand. However, many of the descriptive scientific labels may seem quite complex, so we shall simplify them here.

Polypeptide – Linear polymer of many amino-acids bonded together in a chain, forming part of (or the whole of) a protein molecule.

Glycoprotein – Any proteins that have carbohydrate groups attached to the polypeptide chain.

Permeability Glycoprotein 1 (P-glycoprotein) – A drug transporter protein that plays a role in the absorption, distribution, metabolism, and excretion of drugs via the bile and urine. Its physiological role is the protection of cells in the central nervous system (CNS) from toxic substances or metabolites, which serves to limit drug absorption and distribution. Defective P-glycoprotein function can lead to severe, potentially fatal, adverse drug reactions because of enhanced CNS exposure to drugs (from lack of functional P-glycoprotein at the blood-brain barrier) and/or enhanced systemic exposure to drugs (from lack of P-glycoprotein-mediated biliary and/or renal drug excretion).

Multiple Drug Resistant 1 Gene (MDR1) – The gene that encodes the P-glycoprotein to do its job of limiting entry of toxic substances into the CNS.

As stated by Dr. Katrina Mealy of Washington State University Veterinary Clinical Pharmacology Laboratory (WSU VCPL) , “Defective P-glycoprotein function can occur in dogs and cats with MDR1 gene mutations but can also result from drug-drug interactions. Several commonly used drugs can inhibit P-glycoprotein function, even in animals with normal MDR1 gene structure. Consequently, veterinarians may encounter dogs and cats with intrinsic (genetically mediated) P-glycoprotein dysfunction, as well as with extrinsic, or acquired, P-glycoprotein dysfunction (animals receiving a drug that inhibits P-glycoprotein function)”.

If the MDR1 gene undergoes one or more mutations, it can allow a higher absorption of drugs and toxic substances to enter the CNS which then can breach the blood-brain barrier and create adverse reactions.

Heritable MDR1 gene mutations can affect any dog or cat breed and breed crosses and mixed breeds , but are most commonly found in dog breeds of herding breed ancestry such as the Collie, Long-haired Whippet, Australian Shepherd, Miniature Australian Shepherd, McNab Shepherd, and Silken Windhound. In fact, up to 70% of Collies have the mutated gene, whereas the other commonly affected breeds listed here have MDR1 gene frequencies in descending order of 65-30%. Shetland sheep dogs have this mutation with a 15% estimated frequency. Perhaps surprisingly, the frequency of this gene mutation in Border Collies is low (< 5%).

Fortunately, the WSU VCPL has developed and offers a blood and a cheek swab test to detect the MDR1 mutation. All breeders and caregivers of affected breeds should be encouraged to have this testing done. The test costs less than $100. Compared to the potentially fatal adverse drug reactions these mutations can cause, it is well worth the price.

Does this mean that dogs and cats with the MDR1 gene mutation cannot have any drugs? No; the scientific community has identified many drugs that can and cannot be given to MDR1 affected companion pets. Confounding issues exist, though, that can add to the confusion surrounding this testing:

Dosage level of drug

Drug interactions that may heighten or otherwise alter P-glycoprotein dysfunction

Genes involved

Sample Drugs that cause P-Glycoprotein Dysfunction

Loperamide (Imodium; antidiarrheal agent) – Complete avoidance recommended

Acepromazine (tranquilizer and pre-anesthetic agent) – Reduce the dose

Butorphanol (analgesic and pre-anesthetic agent) – Reduce the dose

Chemotherapy agents (vincristine, vinblastine, doxorubicin, paclitaxel, vinorelbine) – Reduce the dose

Doramectin (antiparasitic)

Erythromycin (antibiotic)

FDA-approved antiparasitic drugs such as ivermectin (Heartgard), selamectin (Revolution), milbemycin oxime (Interceptor) and moxidectin (Advantage Multi) have been tested and found safe for MDR1-affected dogs when given at the prophylactic heartworm preventative dosage level. Higher doses are often prescribed for mange or other conditions and can cause adverse reactions.

If the antiparasitic drug is given with a spinosad (Comfortis; Tri-Fexis), afoxolaner (NexGard), fluralaner (Bravecto) or related flea preventatives, or ketoconazole, itraconazole, fluconazole or related antifungals, then serious drug-drug interactions can occur. It is best to avoid these combinations altogether. Further, these flea preventives are contraindicated for dogs prone to seizure disorders.

Metronidazole is a drug known to cause neurological toxicity and incoordination. But, P-glycoprotein does not transport metronidazole. Metronidazole toxicity, instead, typically results from using it at an increased dose and and/or long duration, and is independent of the MDR1 mutation.

Genetics

Simply knowing if a companion pet has a MDR1 gene mutation is not enough. We need to know if it is present in the homozygous or heterozygous form for both treatment and breeding purposes.

MDR1 Gene Homozygous = mutant/mutant. Affected animals have 2 copies of the mutant allele and always pass 1 copy of the defective gene to their offspring. Homozygotes are more likely to have severe (life-threatening) adverse drug reactions.

MDR1 Gene Heterozygous = mutant/normal. Affected animals have 1 copy of the mutant allele and 1 copy of the normal allele and have a 50% chance of passing the defective gene to their offspring. Heterozygotes tend to have less severe adverse drug reactions.

The ideal situation would to breed only normal/normal dogs and cats. Then again, the MDR1 gene mutation prevalence is so high in some dog breeds that eliminating them from the gene pool likely would entail inbreeding and linebreeding with a resulting rise in prevalence of other heritable conditions such as the autoimmune and other diseases (hypothyroidism and thyroiditis, inflammatory bowel disease, hemolytic anemia and thrombocytopenia, systemic lupus erythematosus, glomerulonephritis, chronic hepatitis, hip and elbow dysplasia, dermatomyositis, cataracts and keratoconjunctivitis sicca). Therefore, sometimes we need to breed a MDR1 gene heterozygous normal/mutant dog to maintain a large enough gene pool. Dogs and cats that are homozygous mutant/mutant for the MDR1 gene should not be used for breeding, as basically they will pass along the MDR1 mutation to all their offspring.

As stated above with respect to MDR1 gene mutations, homozygotes have no P-glycoprotein function, whereas heterozygotes have partial function. So, homozygotes are more likely to have severe life-threatening drug reactions, whereas heterozygotes tend to have less severe drug reactions.

My advice: Get your companion animal tested for the MDR1 gene mutation; particularly if you have a highly affected breed. If your companion pet proves positive for the condition, please find a veterinarian who is up-to-date on the potential drug toxicity issues and can offer sound advice.

W. Jean Dodds, DVM Hemopet / NutriScan 11561 Salinaz Avenue Garden Grove, CA 92843

 References

Mealey, Katrina. "MDR1 Gene Mutations & Drug Therapy." Clinician's Brief, May 2016. Web. 26 Mar. 2017. http://www.cliniciansbrief.com/article/mdr1-gene-mutations-drug-therapy.

"Multidrug Sensitivity in Dogs." VCPL - MDR1 Test. Veterinary Clinical Pharmacology Laboratory, n.d. Web. 26 Mar. 2017. https://vcpl.vetmed.wsu.edu/.

[ask-a-vetblr]

Hi there! Idk if you've answered something like this before but I'm quite curious, is it more common practice these days in veterinary school/medicine for more vets to be aware of how different dog breeds deal with anesthesia and need different doses? Such as how a greyhound or sight hound type dog would differ in amount of anesthesia than say, a german shepherd? I've been reading a book recently, that albeit a bit outdated, seems to emphasise making sure your vet is aware of how the anesthesia differs because "most vets aren't really knowledgeable of how to properly anesthetize a sight hound safely" and I feel like that seems like a bit of a stretch to claim that most dont know how. Thank you so much for your time!

vet-and-wild here.

I can’t speak for every school but we covered it in quite a bit of detail. Different breeds may be prone to certain medication sensitivities as well. To be totally honest though, my experience has been that breeders either don’t fully understand or completely overestimate how important those differences are. Not anesthesia specifically but I had a breeder flip out on me for using Heartgard in an Australian shepherd. For those that are unaware, Aussies and other breeds are prone a mutation in the MDR1 gene, which can make them sensitive to certain meds. Including ivermectin, which is the main ingredient in Heartgard. Except, the doses in heartgard have not been shown to be harmful for dogs with MDR1 mutations. The dose is much lower than say, what you would have to use to treat for mites. Heartgard has been safely used in these dogs for years. So I imagine this breeder is going off about how “vets don’t know about my breed!” when in reality, they don’t understand the full information. There are absolutely breed differences that we need to take into account but at the end of the day, a dog is a dog. Breeders will often insist that there is some special characteristic about their breed but a lot of it ends up being bs.

Not trying to rag on breeders, I have a lot of respect for RESPONSIBLE breeders. I just also have to deal with the results of their half understood science basically every day. Owners who were told their puppy HAD to be on a raw diet and now has raging diarrhea. Owners who are told their breed is sensitive to certain drugs when it’s never actually been recorded in that breed so now an owner is refusing the treatment their dog needs. Breeders who push conspiracy theories about myself and my colleagues and straight up tell owners not to listen to us. Working with a certain breed of course gives you lots of knowledge and experience, but breeding a certain breed for 30 years gives no indication of if a breeder has ever actually read a peer-reviewed article or attended a lecture on canine reproduction.

[sciencehound]

Coated Sighthounds

One thing that baffles me is the #1 guess I get from the general public about what my dog is (besides “long haired greyhound”) is Afghan. Because I’m bored, let’s have a brief (Wikimedia Commons-facilitated) visual discussion of coated sighthounds in the US, shall we?

This is my dog. He’s a silken windhound. He’s an F3 from recent diversity lines (his great-grandmother was a borzoi). He’s over standard, lanky, and has less coat then a lot of people prefer--but he is a silken nonetheless. His rose ears also prick fully when he’s excited. Silkens are a medium-size coated breed, the standard calling for a dog 18.5-23.5 inches at the withers. Their coat is generally not overly dense and may have some wave to it. Brindle is a common color. 

This is Kristull Fallon. He is a bit more typical of what a lot of people are breeding for in the silken breed and apparently represents the breed well enough someone put him as the example dog on the Wikipedia page. He is also my dog’s great-grandsire via that litter with the borzoi. 

This is an Afghan hound. Hairy. VERY hairy. Their profuse, long coat is the most easily recognized feature of the breed. The standard calls for a shorter patch of hair on the back called the “saddle”. They are a large breed, 24-29 inches according to the standard. Brindle does occur.

This is a borzoi, aka Russian wolfhound. They are BIG. They’re a giant breed (27-33 inches) with a medium-long, dense coat that may be wazy, curly, or on the straighter side. Brindle does occur. 

This is a windsprite (formerly known as the “longhaired whippet” and “silken windsprite”). They are a lesser known breed (I mean, what can I say, silkens are too) that has a bit of a controversial history, largely imo thanks to them being referred to as “longhaired whippets” for a significant portion of their history. While some have claimed that the gene for long hair naturally appeared in the whippet breed, the presence of the MDR1 (multidrug resistance mutation 1 aka drug sensitivity)  and CEA (collie eye anomaly) genes in the breed, which are exclusive to collies and related breeds, make their ancestry impossible to deny. According to the International Windsprite Club, they are 16-22 inches tall, making them a small-to-medium breed. While many who don’t know either breed are unaware of the differences, from what I have seen the windsprite coat is generally shorter and less profuse than the silken. Windsprites also generally appear finer of bone with a more prominent stop. They are smaller too. Brindle does occur. They also have can have watermarking, which is very rare in silkens. 

This is a saluki. They are not a truly coated breed, being referred to as “feathered” as the longer coat that exists in the breed is only longer on the ears, tail, backs of the legs, and sometimes the feet and throat. They also some in a smooth coat. They are a large breed at 23-28 inches. Brindle is not allowed in the AKC standard and is a controversial color in the breed (it appears in the country of origin but is considered by some a sign of “contamination” with greyhound blood). But hey guess what. 

This is a Scottich deerhound. It has a wire coat rather than the long coat of the breeds above. It is also a giant breed (28-32 inches). Brindle is common but it usually grays out with age. 

This is an Irish wolfhound. It also has a wire coat. It is also HUGE. It is frequently called the world’s largest dog breed with the standard calling for a minimum of 30 inches for females and 32 inches for males. Brindle is fairly common but, like the deerhound, it generally grays with age. 

Galgos can also come in wire hair. They are a large breed at 24-27.5 inches. They are also pretty rare in the US. They do come in brindle, though. Still more likely you’d see a smooth-coated one. 

There are other coated sighthound breeds, but they are rare and I’d be surprised if they’ve made it to this country.

Non-Sighthounds and not-exactly-sighthounds

Second-generation border whippets (BW x BW) can look an awful lot like a windsprite. Some other lurchers can also have long, feathered, or wire coats depending on what their sighthound and non-sighthound parents are. The same is true of longdogs (sighthound/sighthound mixes). 

Pariah types sometimes get lumped in with sighthounds, but breeds like the Ibizan hound and Portuguese Podengo are very different in temperament from true sighthounds. Also, they are pretty uniformly some shade of red and/or white. And since this whole thing was prompted by my own dog I’ve been emphasizing brindle for a reason. Also those breeds have prick ears. 

[dailypluz]

 8 breeds of dogs with the most serious diseases

Knowledge about genetic diseases in individual breeds of dogs is an important element in the work of veterinarians and breeders. Unfortunately, scientists still have limited knowledge about the frequency of specific diseases in different races. However, advances in technology make it possible to collect more and more data. What is already known?

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Genetic diseases and dog breeding

Genetic diseases are passed on from generation to generation according to different patterns. This means that we are able to predict a certain probability of its appearance.

Breeding of breeds at risk of genetic diseases must only be based on the reproduction of healthy animals. Dogs showing signs of any hereditary disease should be eliminated from breeding. It is best to perform genetic testing before each dog is allowed to breed. They state clearly which dogs are sick.

Performing genetic tests also allows the detection of carriers of specific diseases. A genetic mutation does not always mean disease. Usually, no symptoms of the disease are observed in the case of carriers and there is an option to allow them to breed, but only in combination with a disease-free individual.

The most popular dog breeds are at high risk of genetic diseases

Labrador retriever - in dogs of this breed there are cases of exercise collapse, which is associated with a mutation in the DNM1 gene. Sick dogs are characterized by unsteady gait, lack of power in the limbs, and an increase in body temperature. Proper handling of your dog reduces the risk of seizures. Labradors may also suffer from hip dysplasia and cardiovascular diseases. 

Pug - pugs have a predisposition to various diseases. The most characteristic, however, is the brachycephalic syndrome associated with the structure of their skull and respiratory system. The brachycephalic syndrome consists of such problems as narrowed nasal wings, too long soft palate, tracheal collapse, and laryngeal pockets eversion. Dogs with these defects have breathing problems such as episodes of apnea, coughing, and shortness of breath. Another dangerous disease occurs in pugs, ie pug encephalitis. The disease is genetically determined, difficult to diagnose, and practically incurable. It is possible to perform genetic tests to detect the disease and eliminate such dogs from further breeding.

French Bulldog - Like pugs, bulldogs often suffer from Brachycephalic Syndrome. Genetically conditioned diseases occurring in bulldogs also include cleft palate, cystinuria.

German Shepherd Dogs - Shepherds suffer from around 50 genetic diseases. They are primarily at risk of hip dysplasia, but also von Willebrand's disease, exocrine pancreatic insufficiency, mucopolysaccharidosis type VII, and degenerative myelopathy.

Cocker Spaniel - Genetic testing shows that approximately 11% of dogs have been diagnosed with progressive retinal atrophy. In the studied population of dogs, it was shown that as many as 45% of dogs carried the gene for this disease, which can be passed on to puppies.

Bulldog - is another breed with a high risk of hip dysplasia. It is estimated that the problem affects as many as 73% of the breed representatives.\

Doberman - Dobermans are at high risk of von Willebrand disease, the most common hereditary blood clotting disorder. It is estimated that approximately 49% of dogs carry the defective gene.

Collies - dogs of this breed often suffer from the so-called MDR1 gene mutation. This defect makes dogs sensitive to certain medications, incl. ivermectin or loperamide. This means that preparations with these active substances cannot be administered to dogs of this breed.

How to buy a healthy dog?

When deciding to buy a dog, you should analyze the needs of the breed and genetic predisposition to specific diseases. Then it is worth looking for a proven breeding farm. It is good if it is recommended by a veterinarian or owner of quadrupeds.

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A puppy's parents should be tested for the most common genetic diseases in a given breed. This should be confirmed by documents from laboratories, which we should have access to before buying a dog.

Pedigree dogs are animals that we can learn quite a bit about. The pedigree gives us an insight into the ancestors of our puppy. Such a certificate allows you to estimate the future appearance of the dog, its predispositions, e.g. sports and health. Appropriate selection of the puppy's parents and grandparents increases the likelihood that young dogs will be free from genetic defects.

The price of pedigree dogs is high, but it is worth knowing that there are many costs incurred by the breeder. They include, among others preventive vaccinations, care, and nutrition of bitch and puppies. An important element of the breeder's financial contribution is also the mentioned genetic tests, which are often quite expensive. When buying a purebred dog, however, it is not worth saving or trying to take "bargains". 

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[drferox]

Hi, do you want to talk about collies, especially smooth collies? I'm curious to hear how popular they are on Australia and what's their health situtation there. I love your blog, I learn so much by it.

Smooth and rough collies are lumped together as scotch collies in terms of health. They’re not very common, especially compared to our local herding breeds, but I see a few.

Please note the disclaimer. Theseposts are about the breed from a veterinary viewpoint as seenin clinical practice, i.e. the problems we are faced with. It’s notthe be-all and end-all of the breed and is not to make a judgementabout whether the breed is right for you. If you are asking for anopinion about these animals in a veterinary setting, that is what youwill get. It’s not going to be all sunshine and cupcakes, and isnot intended as a personal insult against your favorite breed. Thisis general advice for what is common, often with a scientificconsensus but sometimes based on personal experiences, and is not aguarantee of what your animal is going to encounter in their life. 

Collie Eye Abnormality is, unsurprisingly, very common in these collies. This is a complex condition where basically parts of the back of the eye are underdeveloped. Severity will vary between individuals, with the worst cases being blind. It’s genetic, but so common in rough collies that selective breeding to eradicate it will be difficult without outcrossing.

The mutated MDR1 gene was more common in this breed too. This gene is responsible for the persistent belief that collies should not be given ivermectin or heartworm prevention. This gene alters the permeability of the blood-brain barrier allowing certain drugs, including ivermectin, to enter the brain at much lower doses and do seriously bad things. You can test for this gene, and should if the parents have not been tested themselves, because it’s not just ivermectin that’s the problem, but several other drugs as well. Also, there are heartworm preventatives available that are safe for dogs with this gene, so confirm what’s available with your vet.

The breed is large enough to occasionally present with gastric dilatation volvulus, where the stomach twists on itself, cutting off blood supply. Epilepsy  and hypothyroidism are also reported to be more common in these dogs.

Canine Cyclic Neutropenia is a rare but nearly unique condition of rough collies. It’s also known as Cyclic Haematopoesis or Gray Collie Syndrome. This is a recessive genetic disorder that causes neutrophils, white blood cells which are the first line of defense, to drop dramatically in numbers every 12 days or so, leaving the dog very vulnerable to all sorts of infections. This is a dramatic but rare condition, and my understanding is that there have been attempts to eradicate it, aside from some colonies of research dogs used to study related human conditions.

[the-pasta-pack]

TFW your Silken is MDR1 clear but you're not.

Not the same mutation but the same gene. Apparently I'm 7x less likely to respond positively to certain antidepressants and more likely to suffer negative side effects because of the way that they travel through the blood-brain barrier (which is the same reason MDR1 affected dogs can't take certain drugs).

This is kinda amazing tbh.

[canisitsnotlupus]

@lvtsoulstice                                                                                                        “This is a tangent, feel free to make a separate post in response to this but– MDR1 isn’t a problem in BCs? We’ve been doing pharmacology in vet tech classes and collies in general were mentioned for ivermectin sensitivities (more likely to cross the blood-brain barrier etc) due to the MDR1 gene, BCs were included. Border collies aren’t more likely to be sensitive to ivermectin?” From the research I have done with various friends, MDR1 is very rare in BCs. They are generally included solely because they are of the ‘collie’ type, and if I remember correctly, the only dogs that came up positive for it that was labeled ‘BC’ were dogs that were not proven BCs, ie, likely to be mixed. The theory (BC circle, at least) was that given the breed’s primary function as a sheep dog, whereas most other breeds exhibiting the MDR1 mutation were cattle dogs, basically became housepets, or were from other collie lines, was that natural selection took affect. Dogs with MDR1 ate ivermectin poop, or were treated with it, died. Farmers soft culled (or in some cases, hard culled) the parents and siblings out of worry, and thus, eliminated the gene early on. BC’s close cousin, the Old English Sheepdog, is also incredibly low - likely for this same reason. Collies, which were from the same landrace as those two (as well as the others), were quickly turned to more of a housepet/showy type dog, and thus, may not have had selection play its part. I don’t know collie history enough to verify this, I just know this is the rumor around the BC folks when this is brought up. You can see a bit on it on the BCboards linked below. “The Mutation of the ABCB1 gene associated with multidrug resistance 1 has been identified in the Border Collie. Though the exact frequency in the overall Border Collie population is unknown, in North America 1.3% out of 306 Border Collies were carriers and 0.3% were at-risk. In Europe, none of the 116 Border Collies tested in one study had inherited the mutation. Worldwide, the percentage of carriers ranges from 0% to 5% and the percentage of Border Collies at-risk for MDR1 ranges from 0% to 0.4%. “ - Pawprint Genetics. https://www.pawprintgenetics.com/products/tests/details/93/?breed=34 - 1%. http://vcpl.vetmed.wsu.edu/affected-breeds - Under 5% http://www.wisdompanel.com/mdr1_disease_screening/ - Under 5% http://www.bordercollie.org/boards/index.php?showtopic=4966 - No BC has been found with the MDR1 mutation of proven lineage. http://www.pnas.org/cgi/reprint/101/32/11725 - Actual report the above link refers to.

[cvdogclub]

Is your pasture/barn safe for your dog?

Many of us dog lovers also spend time with our Equine companions. Sometimes we even do this as a canine, equine, and human team. From trail riding to shows, to camping and trips to the beach. We all know the safety issues with dogs and horses. Potentials for: bites to the horses, kicks to the dogs, dogs ingesting horse feed. But who ever stops and thinks what if fido eats manure from my trusty steed? Sure you think of catching a possible parasite from a horse that is a carrier, but did you know that Ivermectin, the most common horse dewormer, is actually extremely toxic to many dogs. Predominantly found in traditional herding breeds but does also include German Shepherds (yes they are a herding breed), Long haired Whippet, and Silken Windhound is a genetic mutation called MDR-1.

What does MDR 1 mean? It means that the blood brain barrier present In mammals that ensures things such as anti-parasitic medications, many sedatives, and certain antibiotics do not start to attack the brain, does not exist.

This is a simple and inexpensive genetic testing that could end up saving your dog’s life and saving you a decent amount of money. You see a blood brain barrier acts basically as a valve. It lets a little medication in but then lets it right back out another exit. Without this barrier the medication builds up. When certain medications such as antibiotics and anti parasitics build up in the brain they start to attack your dogs brain. This can cause a variety of symptoms with the most common being: dilated and fixed pupils, blindness, inability to stand or walk, heavy breathing, lethargy, depression, excessive drooling, convulsions, vomiting and diarrhea.

The following scenarios describe where a dog could access ivermectin in relation to horses. If your dog eats manure from a horse treated within the last 30 days. If your dog walks through a feed through ivermectin and ingests pellets or eats the pellets direct, if your dog walks though or eats saliva of a horse that contains the ivermectin dewormer, if your dog accesses a tube of horse or livestock dewormer and chews on it; used or full.

Now we discuss how they could access ivermectin when they are never near horses. Your dog could be prescribed Heartguard, Sentinel, or Iverheart which are all routine monthly heartworm preventatives. Your dog could need heartworm treatment and the go to is ivermectin at a high dose. And Sentinel is used to prevent flea eggs from developing and as already discussed is an ivermectin based product. Several over the counter feed store dewormers for dogs also include ivermectin.

The biggest thing to note if your dog does get into ivermectin is to get to the vets office immediately before symptoms show if possible. Also call the Pet Poison Helpline 1-800-213-6680. There is a cost for both people and animal poison control but their veterinarians, toxicologists, and pharmacists can help and talk directly with your vet and come up with a treatment plan that your veterinarian, no matter how wonderful and well educated, may not know about new treatment methods. Lipids for example was something that when I went through this with my own dog Calli, I knew nothing about. I found no information online about it but Poison control and my Veterinarian talked and their facility did not know either. We tried it and it worked. Is it worth the $45.00 to help save her life....Absolutely!

But if you     find yourself with a breed susceptible to MDR1 it is worth it to do a DNA     test to see if they have the mutation. The list of medications your dog     could have adverse reactions to is lengthy but includes:

Acepromazine

Butorphanol

Doxorubicin

Doramectin

Emodepside

Erythromycin

Ivermectin

Loperamide

Milbemycin

Moxidectin

Paclitaxel

Rifampin

Selamectin

Vinblastine

Vincristine

While Ivermectin is usually the calling card that brings this unfortunate message to a dog and their human there are many other medications that will cause the same life threatening condition. The best part is there is testing you can do if you want to make sure if your dog has this gene or not. Many reputable breeders will test parents and puppies of certain breeds to ensure that their gene pool is free from this mutation, but owners can do this too.

Wisdom Panel for example provides a simple genetic test that does not break the bank and can let you know if your dog has this condition. Further if you want to forego this testing you can list with your vet that you do not want any of those medications used on your dog and you want your dog treated as if they have the MDR1 genetic mutation.

In my personal experience my 10 ½ year old German Shepherd who I adopted when she was 18 months and is my sons service dog, walked onto saliva from my horses with ivermectin in it and licked it off her paw. She sustained a chemical burn on her paw and within hours was blind, unable to walk, stand, had labored breathing, and excessive drooling. She was the first at her wonderful Banning Animal Hospital clinic to have a lipid treatment recommended by Poison Control. She had a 4 day vet stay, and overcame everything. She has fully recovered and you would never know anything had happened. But it was nerve wracking for our entire family and something I had never expected. I was always diligent that horse meds and feeds were kept secure from the dogs but never though she could have ingested such a small amount with such dire consequences.

[thepetsworld]

The English Sheepdog Puppies Breeders Raise Are Wonderful Pets For The Right Families

By Pamela Wood

Some animal lovers, who have really good intentions, get carried away when they see a litter of puppies that are ridiculously cute. They don't think about how big the puppy will get, how much attention it will need, or whether or not they have room in their house or the money their budget to make an appropriate home for the adult dog. This is a frequent problem when families first set eyes on the sheepdog puppies breeders sell. It would be hard to beat one of these puppies for cuteness. They look like furry stuffed animals that have magically come to life. They are real however, and will eventually grow to nearly two feet in height and a hundred pounds in weight. Sheepdogs have a lot of energy and require a great deal of attention. They are boisterous, energetic, and love to play. Unless you own a house with a big backyard or a place in the country, it will be hard to contain these dogs. You won't have to take them for a twenty mile run each day, but they do need a good hour or two of serious exercise with plenty more free time just playing. All you have to do is take a quick look at one of these dogs to know that grooming is a big part of ownership. They must be brushed and combed regularly to prevent matting. You will have to keep the hair around their eyes cut so they can see where they're going. Some OES owners have the coats trimmed to avoid the time and hassle of constant grooming. Like most purebred dogs, the sheepdog can inherit a number of diseases and conditions. A reputable breeder will be able to tell you about the genetic makeup of the puppy you are considering. Some sheepdogs inherit deafness, hip dysplasia, and eye problems. They can also inherit a gene mutation known as MDR1, making some medication lethal. When you are weighing the pros and cons of purchasing one of these puppies, there are several factors to consider. If you don't have the time or inclination to groom your animal, you should pass on an OES. Individuals who are bothered by a dog that can be strong willed and loves to jump on people should choose another animal. If, on the other hand, you don't mind your dog tracking in dirt, mud, and grime, or one that is a messy eater, the OES could fit into your home. If you have the time to groom your animal, and aren't looking for a guard dog, this may be the animal for you. Almost all baby animals are cute. They do grow up however, and they are all individuals with specific personalities and attitudes. When you bring a puppy into the family, you have to consider your lifestyle and the needs of the dog. Animals end up in shelters every day because owners didn't think before they bought a pet that was unsuitable for them.

About the Author:

You can get a summary of the things to keep in mind when buying Old English Sheepdog puppies at http://ift.tt/2wkivnE right now.

The English Sheepdog Puppies Breeders Raise Are Wonderful Pets For The Right Families via zoologist01 http://ift.tt/2AAZYEX

[paulcleonard]

Border Collie

Border Collies are best known for their intelligence and working roles as sheep herding dogs.

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Border Collies are a highly intelligent breed and need lots of exercise and training. If you are thinking about owning a Border Collie be prepared to spend in excess of 2 hours a day with your dog keeping that intelligent mind occupied. These dogs need lots of space, games, puzzles and ideally a job or sport to do, like agility or farm work.

Border Collies really do need an experienced owner who loves to train and someone very active. In exchange a Border Collie will be responsive, loving and fun to share your life with.

WHAT DOES THE BORDER COLLIE WANT IN THEIR PERFECT LIFE PARTNER/FAMILY?

I’m looking for an owner as active as I am. Someone who loves a run at the beach, playing ball, training and agility or flyball. I would love to live on a big property with lots of other dogs and people. I bore easily, so I really need to be kept busy and I do not like to be alone. Please remember I love to herd and if you don’t have anything for me to do, I will round up the family!

AT A GLANCE

Lifespan 10-15 years Weight 12-20 kg Height (at shoulder) 50-53 cm

  PERSONALITY

Playful – Life is just a game to your average Border Collie. They love chase, ball-games and playing with other dogs. As they get older they can become a little lazy, but if kept at a healthy weight will often stay playful into middle age.

Lively – Border Collies are very active dogs and need lots of activity and stimulation. They are often very excitable, particularly when their owners come home.

Loyal – A Border Collie will often bond very closely to one person in the family and be extremely loyal. This can translate to a dog that is not suited to long periods of being alone and perhaps even a bit snappy if not socialized appropriately.

Intelligent – These intelligent dogs are very trainable and need at least 2 hours a day of exercise and training when young and continuing on into adult-hood. Without mental stimulation and training they become easily bored and sometimes destructive.

EXERCISE & TRAINING

Exercise Requirements Very High – 2+ hours per day Training Requirements Very High – 2+hours per day or working dog (eg property or assistance dog) Apartment Friendly? No

  Border Collies are high energy dogs that need lots of exercise and training. An activity like agility, flyball, obedience work or dancing would be ideal. If you live near a beach or on a property and have lots of spare time, the Border Collie would be a good fit.

GROOMING

Trips to the Groomer No- easy care at home Tick Friendly? No Hypoallergenic No Brushing High – Daily brushing required Hair fall High Shed – you will be living with lots of hair Coat Type Long

  Border Collies really need a daily brush or to be clipped regularly as they have a dense coat that can be high maintenance. They are ideally suited to colder climates, rather than hot climates, but their coat can also be insulating in warmer conditions. Just make sure there is a dam or pool to jump into on hotter days if you live somewhere with hot summers.

FAMILY SITUATION

Good With Kids Excellent – Good with kids of any age Good With Other Small Pets Medium – Ok with other pets, supervision advised Sociability High – Loves other dogs and best in a multi-dog household.

  Border Collies are ideal dogs for multi-dog households. Having a canine playmate can help to alleviate boredom and burn off some of that boundless energy. They are generally okay with kids, but are often very busy dogs so need their own space and can be very excitable as young dogs. An adult Border Collie tends to be very gentle with young or older kids if socialized when young. Border Collies do have a tendency to ‘herd’ other pets such as cats, so if they are not given an outlet for this behavior, they should be watched around smaller animals inclined to scare easily.

EXPENSES

Overall Expenses (Annual) Medium – $1500-$2000 Veterinary Expenses (Annual) Medium – $200-$500 Food Expenses (Weekly) High (large and giant) – $20-$30+

  Border Collies tend to be robust, healthy dogs who don’t have large health problems. That being said they do often put 110% effort into activities and can easily injure themselves in the process. They also need good quality food and lots of it to power that energy house.

HEALTH & WELLBEING

MAJOR HEALTH CONCERNS

Ivermectin sensitivity – first described in 1983 some Collies are uniquely sensitive to ivermectin, which is used for parasite treatment. The MDR1 gene mutation that causes this sensitivity can be tested for. Those dogs with the mutation should be given ivermectin containing medications with caution and may be more susceptible to loperamide, digoxin, odansetrom and many chemotherapeutic drugs also.

Hip Displaysia – Border Collies are prone to hip dysplasia, and while more breeders are hip scoring in an attempt to breed out this devastating disease, in some cases it can still occur, particularly with overfeeding at a young age.

OCD – Osteochondrosis Dissecans is a painful cartilage defect that occurs in large breed puppies and commonly involves the shoulder joint, but can also effect the elbows, knees or ankles (hocks). Like hip dysplasia it has been linked to over-feeding during the growth phase and excess calcium supplementation.

PREVENTATIVE CARE & WHAT TO LOOK FOR:

Border Collie breeders are usually very proactive in testing for the genetic diseases Collie Eye Anomaly/Choroidal Hypoplasia, Neuronal Ceroid Lipofuscinosis and Trapped Neutrophil Syndrome, but you should check with your breeder before buying a Border Collie on the status of their dogs for genetic diseases.

Border Collies are not ideally suited to areas with ticks or seeding grass, due to their long coat. However if regularly brushed or clipped they can be a little easier to manage.

Border Collies should be fed a high quality diet and an appropriate ration should be determined to ensure they are not over-fed when growing to reduce the chance of hip dysplasia and OCD. They are also more inclined to develop cruciate ligament rupture and other orthopaedic injuries if allowed to become overweight.

BREED ORIGIN AND INTERESTING FACTS

Border Collies are all descended from a dog in Northumbria in the north of England called Old Hemp who was a legendary sheep dog. His fame and skills meant that he sired large numbers of puppies for farmers who wanted excellent sheep dogs. Sheep dogs typically need to be fast, stealthy and intelligent. They should be able to read sheep, respond to hand signals and love to work and herd sheep.

The bronze statue that stands at Fort Benton Montana, US was erected for Old Shep who kept a 6 year vigil for his owner who died in the town. Legend has it that Old Shep saw his owner’s coffin being loaded onto a train after he died in hospital and from then on he met each train coming in, waiting for his owner to return. Sadly he was hit by a train and died in 1942.

The Border Collie is ranked at number one in Stanley Coren’s The Intelligence of Dogs.

Owners of working Border Collies may be reluctant to own a white dog as it is thought that the sheep would not respect a white dog.

RESCUE A BORDER COLLIE

Petfinder lists all types of dogs who need homes, both purebred and mixed breeds, adults and puppies.

Border Collie Rescue has Border Collies across most of the US needing new homes.

Border Collie Society of America also coordinates fostering and rescue of Border Collies US-wide.

The ASPCA often has Border collies for adoption, just do an advanced search on their adoption page.

  The post Border Collie: Breed Information appeared first on Love That Pet.

[cancersfakianakis1]

Mechanisms of Pinometostat (EPZ-5676) Treatment Emergent Resistance in MLL Rearranged Leukemia

DOT1L is a protein methyltransferase involved in the development and maintenance of MLL-rearranged (MLL-r) leukemia through its ectopic methylation of histones associated with well characterized leukemic genes.  Pinometostat (EPZ-5676), a selective inhibitor of DOT1L, is in clinical development in relapsed/refractory acute leukemia patients harboring rearrangements of the MLL gene. The observation of responses and subsequent relapses in the adult trial treating MLL-r patients motivated preclinical investigations into potential mechanisms of pinometostat treatment emergent resistance (TER) in cell lines confirmed to have MLL-r.  TER was achieved in five MLL-r cell lines, KOPN-8, MOLM-13, MV4-11, NOMO-1, and SEM. Two of the cell lines, KOPN-8 and NOMO-1 were thoroughly characterized to understand the mechanisms involved in pinometostat resistance. Unlike many other targeted therapies, resistance does not appear to be achieved through drug-induced selection of mutations of the target itself.  Instead, we identified both drug efflux transporter dependent and independent mechanisms of resistance to pinometostat.  In KOPN-8 TER cells, increased expression of the drug efflux transporter ABCB1 (P-glycoprotein, MDR1) was the primary mechanism of drug resistance. In contrast, resistance in NOMO-1 cells occurs through a mechanism other than upregulation of a specific efflux pump.  RNA-seq analysis performed on both parental and resistant KOPN-8 and NOMO-1 cell lines supported two unique candidate pathway mechanisms that may explain the pinometostat resistance observed in these cell lines. These results are the first demonstration of TER models of the DOT1L inhibitor pinometostat and may provide useful tools for investigating clinical resistance.

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[drferox]

BORDER COLLIES! Because I love them but recognize they got them problems (also they everywhere). Came for the tonnes of vet stuff, stayed for the tonnes of vet stuff... and the sassyness ;)

Ah, the Border Collie. Shot to fame by certain celebrity vets and movies like Babe. They are certainly very common pets, but very uncommon working dogs around here (Australia).

Please note the disclaimer that these posts are about the breed from a veterinary viewpoint as seen in clinical practice, i.e. the problems we are faced with. It’s not the be-all and end-all of the breed and is not to make a judgement about whether the breed is right for you. If you are asking for an opinion about these animals in a veterinary setting, that is what you will get. It’s not going to be all sunshine and cupcakes, and is not intended as a personal insult against your favorite breed. This is general advice for what is common, often with a scientific consensus but sometimes based on personal experiences, and is not a guarantee of what your dog is going to encounter in their life.

There are a number of likely inherited problems present in this breed, as well as a few concerns which are likely more to do with environment than anything else.

They are collies, so it;s not entirely unexpected that they can get Collie Eye Abnormality (CEA) and several other eye conditions. Overall they don’t seem to be too severe, but it’s not uncommon for these dogs to go blind in their later life. Blindness is not necessarily the end of the road for a dog in a stable environment though.

Some of these dogs will also have a mutation in the MDR1 gene, which is best known for producing a sensitivity to ivermectin. This is the reason some border collie people say not to use certain parasite products on border collies. This risk is probably overblown because the mutation is not all that common, and not every active ingredient in parasite products is going to be an issue for affected dogs anyway. There are genetic tests available these days, and I think they often are worth doing because there are other drugs, not just ivermectin, that dogs with this mutation are extra sensitive to.

And while you’re getting that genetic screen done, you’ll find out whether the dog has or carries cerebellar abiotrophy, a rapidly degenerative brain disorder. It’s rare, and should be being bred against, but still exists.

Epilepsy might, possibly, be inherited in this breed. It’s hard to pin this down though because there are multiple different types and patterns of epilepsy which are not as well understood in dogs as they can be in humans, because I can’t ask a dog what’s going on in their head before or after, I can only observe.

In terms of the environment, I’ve spent several Summers pulling grass seeds out of these dogs. They especially hate them in their feet, and they don’t forget what’s done without sedation.

Cruciate ligament tears are the most common orthopedic injury I see. Active dogs, running and twisting, jumping off things is a common way to teat them. Another common presentation is older dogs who used to be active, but are now much heavier than they should be, and the extra strain on the ligaments can cause them to tear with relatively little effort.

Adult Onset Demodex Mange is an odd condition that for some reason I have encountered most in border collies. It’s not all that common overall, but I seem to see it in this breed in particular. While juvenile demodex is relatively common, adult onset demodex is rate because it occurs when a dog previously had a healthy immune system, but now does not. The classic reasons being extended high doses of cortisone or lymphoma. In short if a dog develops demodex mange as an adult, something is probably very bad.

This breed benefits from lots of exercise and mental stimulation. They are still a working breed, even if they are popular pets.

The Mental health aspect of this breed shouldn’t be ignored either. While they’re characterized and popularized as intelligent, willing dogs they can also become neurotic and fearful. This can happen even with ideal upbringing situations and I haven’t met many border collies that seem to completely relax like other breeds can. My worst anxiety patient is a border collie, you can’t even stand in a closed room with him without freaking out and we’ve had to reschedule many appointments due to the dog’s sheer panic. He’s lucky to have willing owners that are prepared to work around his problems, otherwise I suspect he would have either been put to sleep long ago or had a substandard quality of life.

I think the possible unstable temperament is a result of the breed having a surge in popularity and a period of being indiscriminately bred to meet demand, as I think has also happened with German Shepherds, Dalmatians and Cocker Spaniels, for example.

[ronaldmorton]

How to Test Your Dog for Genetic Diseases

Science has come a long way, and that includes cutting edge insights into the health conditions that might affect our beloved dogs. Imagine if you could test your dog for genetic diseases whether that dog is from a rescue, a shelter, a foster, or a breeder. Imagine that during that genetic screening that you could determine your dog’s ancestry, as in what breeds comprise your dog.

The folks at Embark asked if we would do an honest review in exchange for a DNA/genetic testing kit. The Embark dog DNA test is something I wanted to try, so this provided a perfect opportunity. This dog DNA home test kit is touted as the most sophisticated genetic test available for consumers that -with one cheek swab – and gives U.S. dog owners spot-on scientific insight into their pets’ health, behavior, ancestry and more.

Count us in. Here’s our experience and why you should consider the Embark dog DNA test for your dogs.

Meet the Bark Behind Behind Embark

Adam and Ryan Boyko are the brains behind both the product and the start—up tech company called Embark. Adam, a world-reknown expert in canine genetics, is assistant professor in Biomedical Sciences at the Cornell University College of Veterinary Medicine. His brother, Ryan, is a Harvard and Yale graduate who traveled the world collecting dog samples and contributing to a number of prominent scientific studies about canine health. Partnering with Cornell University College of Veterinary Medicine, the leading veterinary school in the country, and Spencer Wells, a pioneer in consumer genetics, the Boykos founded Embark.

The Process

Once you purchase the Embark DNA Home Test Kit, a package will be mailed to you. In it, you will find what you need to simply swab the inside of your dog’s mouth, activate your kit, and send the sample in a prepaid envelope to the Embark lab. It is that easy. You want to be sure your dog does not eat or drink for about 30 minutes before getting the saliva sample, which is super easy to obtain. I had my spouse hold a piece of a favorite dog treat near Dexter and he soon salivated and I was able to swab the inside of his mouth and get the sample. Instructions are provided. Here’s everything you get, including a cute and purposeful dog tag:

How is Embark Different From Other Dog DNA Tests?

This is one of the first questions I had, and you can read a dog this for a dog DNA test comparison.  I also liked the email updates I received from Team Embark, a sampling is below. The folks at Embark say this test screens for over 160 genetic health conditions, the most accurate breed identification scientifically possible (based on more than 100 times as much genetic information as other tests), and so much more.

What Kind of Dog Genetic Diseases?

MDR1, degenerative myelopathy, dilated cardiomyopathy, PRA blindness, exercise-induced collapse and more, using 200K + genetic markers for over 160 diseases. Information revealed in the tests can help an dog parents perfect their dog’s diet, for instance, to address needs not specific to the breed but to that exact animal.  The kit is also designed so you can discuss your results with your veterinarian and it can actually potentially change how your vet would treat certain conditions if they developed.

Personally, having the results gives me peace of mind. Cocker Spaniels have their own share of genetic anomalies, and as I mailed off the saliva sample in the prepaid envelope, I knew having the results would help my dog receive better care. This information you will receive comes as a Vet Report, designed specifically for dog parents to bring to their vets to help guide healthcare decisions. Knowing a dog’s genetic predisposition for a disease may help you take precautionary measures and know early warning signs to watch for, so this is a plus.

Fidose Goes to Science

If you like to geek out as I do and understand what the process of the saliva and extraction involves, here goes in a condensed nutshell, from the folks at Embark to me in an email:

First, our team separates Dexter’s DNA from everything else that the sponge soaked up. Our scientists delve into Dexter’s cells with chemicals and awesome machines called centrifuges and pull out all the doggy DNA they can. Then the sample goes through several steps of purification to remove everything else. Next our team pops the DNA in a PCR machine which makes lots of copies of your dog’s DNA — we’re talking millions of copies of DNA from a single cell. Without the PCR machine, we might have needed a gallon of saliva from Dexter to get the DNA profile, and nobody wants that. Seriously, this machine is amazing! After that comes the genotyping, which we will tell you about in our next email.

The Results

The whole process takes one to two months, on average, which can seem like forever, but it is oh so worth it. Ours took about a month.

From a DNA perspective, our dog is 100 percent all-American Cocker Spaniel, with a 1.7 percent factor of “wolfiness.” We are told that Cocker Spaniels are handsome and intelligent hunting dogs that are also well suited to life as a loving family pet.

Wolfiness Factor

We totally dig this number: How wolfy is our dog? If you ever wanted to know how much wolf is in your dog’s DNA, they tell you! Most dogs have wolfiness scores of 1% or less, although Embark says they occasionally find populations and breeds with higher scores and even some especially unique individuals with scores of 5% or more. Our pup is 1.7 percent. Aroooo!

What Wolfiness Means For Your Dog

Your dog’s Wolfiness Score is not a measure of recent dog-wolf hybridization (the breed mix analysis report would tell you if your dog has any recent wolf ancestry). Instead, the wolfiness score is based on the number of wolf genetic markers your dog has in our unique wolfiness marker panel. While these wolf genes (or, more scientifically speaking, alleles) could be in your dog because it is a wolf-dog hybrid, wolfiness scores below 10 are almost always due to ancient wolf genes that have survived many generations to be carried in your dog. These may date back to the original domestication event 15,000 years ago or to more recent dog-wolf matings only a few thousand years ago, but either way they are bits of a wild past that survive in your dog!

Health Markers

Alas, the big question: What exactly did our health screening show for our dog, Dexter?

Alanine Aminotransferase Activity result: Low Normal

Dexter has one copy of a mutation associated with reduced ALT activity as measured on veterinary blood chemistry panels. Please inform your veterinarian that Dexter has this genotype, as ALT is often used as an indicator of liver health and Dexter is likely to have a lower than average resting ALT activity. As such, an increase in Dexter’s ALT activity could be evidence of liver damage, even if it is within normal limits by standard ALT reference ranges.

Carrier Condition: Skeletal Dysplasia 2 (COL11A2): A disease of skeletal development, this causes dogs to have abnormally short legs but similar body lengths compared to unaffected dogs, and can be observed by the time dogs reach five to six months of age. This has been best characterized in certain lineages of Labrador Retrievers. Other than their height, affected Labradors suffer no ill effects from their condition. However, affected dogs nearly never meet breed standard.

Most notably, he tested clear for all the diseases for which they screened! YAY. I have peace of mind. Each of those diseases is outlined in a fully detailed online report AND they would even send a copy to my dog’s veterinarian.

More to Come

Embark says their scientists are hard at work in the lab, and they are expanding our results all the time! As new features and results become available they will let me know.

How to Purchase an Embark DNA Kit

Simply click the photo below and learn more about Embark DNA and purchase your dog’s very own Embark DNA and genetic testing kit.

or

CLICK THIS: Embark Dog DNA Test · Breed Identification · 160 Health Results · 200K Genetic Markers

Have Two Dogs? There is a discount on the price of two Embark Dog DNA tests here:  Embark Dog DNA Test 2 Pack: Most Accurate Mixed Breed Identification With Over 160 Health Tests

Win an Embark Dog DNA Kit

We are giving away one Embark Dog DNA and Genetic Testing Kit to one lucky Fidose of Reality fan. Visit the entry form below for your opportunity to win a kit: (complete rules and regulations here, and USA only, 18 and older) a Rafflecopter giveaway

Note: We are a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for us to earn fees by linking to Amazon.com and affiliated sites.

The post How to Test Your Dog for Genetic Diseases appeared first on Fidose of Reality.

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