Double muscling

The MSTN gene provides instructions for making a protein called myostatin. This protein is part of the transforming growth factor beta (TGFβ) superfamily, which is a group of proteins that help control the growth and development of tissues throughout the body. Myostatin is found almost exclusively in muscles used for movement (skeletal muscles), where it is active both before and after birth. This protein normally restrains muscle growth, ensuring that muscles do not grow too large. Myostatin has been studied extensively in mice, cows, and other animals, and it appears to have a similar function in humans.

At least one mutation in the MSTN gene has been found to cause myostatin-related muscle hypertrophy, a rare condition characterized by increased muscle mass and strength, animals with such mutation are described a “double-muscled”.

These animals do not actually have two muscles, but each muscle is significantly larger than normal. Double-muscled animals have an incredibly muscular look even if they do not exercise. This mutation is of particular interest in species farmed for their meat (like cattle) but can occur in any mammal.

Myostatin mutation is studied in a line of mice called the “Mighty Mouse”. These mice were developed as a side effect of a line of research at the Johns Hopkins School of Medicine when they inactivated or “knocked out” a gene responsible for producing myostatin.

“Mighty mouse” next to common relative.

mightymouse_x600The myostatin mutation is particularly valued in cattle and is a recessive trait often found in the Belgian Blue, Piedmontese, and Marchigiana breeds–but present in many other breeds.


Confirmed mutation in MSTN found also in the whippet dog breed that results in a double-muscled phenotype known as the “bully” whippet (“A Mutation in the Myostatin Gene Increases Muscle Mass and Enhances Racing Performance in Heterozygote Dogs”, 2007). During this research study were screened also several mastiff type breeds (rottweiler, bulldog, Presa Canario, miniature bull terrier, American Staffordshire terrier, Staffordshire bull terrier, and bullmastiff) without any findings.



Research: Gene associated with canine atopic dermatitis

A novel gene associated with canine atopic dermatitis has been identified by a team of researchers led by professors Kerstin Lindblad-Toh, Uppsala university and Ake Hedhammar, SLU, Sweden. The gene encodes a protein called plakophilin 2, which is crucial for the formation and proper functioning of the skin structure, suggesting an aberrant skin barrier as a potential risk factor for atopic dermatitis.

Details appear in the open-access journal PLoS Genetics.

Atopic dermatitis (or eczema) is an inflammatory, relapsing non-contagious skin disease affecting about 10-30 percent of the human population. It is not only humans that suffer from the disease: about 3-10 percent of dogs are also affected. The skin of a patient with atopic dermatitis becomes easily irritated by various allergens such as certain types of food, pollens or house mites. Such irritation causes very strong itching which leads to scratching, redness and flaky skin that becomes vulnerable to bacterial and yeast infections.

To-date, despite many scientific efforts, little has been known about the genetics of the disease. In their study, researchers from Uppsala University, SLU and Broad Institute, compared DNA samples from a large group of German shepherd dogs affected by atopic dermatitis with DNA coming from healthy dogs to reveal the specific DNA segment associated with the disease.

“With the help of pet owners, we have managed to collect a unique set of DNA samples from sick and healthy dogs which allowed us to gain insight into atopic dermatitis genetics,” said first author Katarina Tengvall, Uppsala University.

Purebred dogs such as German shepherds have been selected for specific physical features for several generations. Selection led to an inadvertent enrichment for disease-risk genes in certain breeds. Moreover, the resulting architecture of canine DNA makes it easier to pinpoint segments that carry these disease risk-genes. This helped the researchers to reveal the genetics of atopic dermatitis. They found a region associated with the atopic dermatitis containing the gene PKP-2, which encodes Plakophilin-2, a protein involved in the formation and maintaining of the proper skin structure.

“The finding that certain variants of the PKP-2 gene may increase the risk of developing the disease opens new possibilities in understanding the disease mechanism leading to atopic dermatitis,” continues Katarina Tengvall.

These findings will not only lead to better understanding of the disease, which may lead to better treatment strategies long term. It also opens up the possibilities of development of a genetic test for the disease.

“Our study suggests that plakophilin-2 and an intact skin barrier is important to avoid atopic dermatitis”, says senior author, Kerstin Lindblad-Toh, professor at Uppsala University and Director of SciLifeLab Uppsala. “Another gene involved in the skin barrier has recently been linked to human atopic dermatitis emphasizing the similarity between canine and human atopic dermatitis” continues Kerstin Lindblad-Toh.


Multi-drug Sensitivities in Dogs

A number of dog breeds are more prone to serious side effects from certain drugs than other breeds. For example, Collies can have severe adverse reactions to the antiparasitic drug, ivermectin.
The cause of this sensitivity is a DNA sequence change (mutation) in the dog’s multi-drug resistance gene, known as the MDR1 gene. The function of this gene is to prevent dangerous drugs from entering the CSF. Dogs with the mutated MDR1 gene have an alteration in the blood brain barrier affecting transport of drugs such as ivermectin. Exposure to these drugs may result in serious neurological signs, such as hypersalivation, ataxia, blindness, tremor, respiratory distress and even death.
As well as protecting the brain, the MDR1 gene plays a vital role in drug elimination. Dogs that have a
mutated MDR1 gene can have reduced drug elimination compared to others, resulting in elevated plasma drug levels and an increased tendency for toxicity.
A number of drugs have been shown to cause problems in dogs with a mutated MDR1 gene.
These include:
Acepromazine (tranquilliser)
Butorphanol (analgesic)
Cyclosporin (immunosuppressant)
Digoxin (cardiac inotrope)
Doxorubicin (antineoplastic)
Ivermectin (antiparasitic)
Loperamide (antidiarrhoeal)
Vinblastine (antineoplastic)
Vincristine (antineoplastic)
(Please note that this is not a complete list of drugs that may affect dogs with the MDR1 gene mutation)

Approximately 75% of Collies in Australia have the mutated MDR1 gene. The mutation has also been found in Shetland Sheepdogs (Shelties), Old English Sheepdogs, German Shepherd Dogs, Long-haired Whippets and a variety of mixed breed dogs.

You can test your dog for multidrug sensitivity and prevent serious adverse drug reactions.

Washington State University
Gribbles Molecular Science and Gribbles Veterinary Pathology

Popular-Sire Syndrome in purebreds

 Syndrome:  Keeping watch over health and quality issues in purebreds

Jerold S Bell, DVM, Tufts Cummings School of Veterinary Medicine
(This article originally appeared in the “Healthy Dog” section of the August, 2004 AKC Gazette)

An important issue in dog breeding is the popular-sire syndrome. This occurs when a stud dog is used extensively for breeding, spreading his genes quickly throughout the gene pool. There are two problems caused by the popular-sire syndrome. One is that any detrimental genes which the sire carries will significantly increase in frequency – possibly establishing new breed-related genetic disorders. Second, as there are only a certain number of bitches bred each year, overuse of a popular sire excludes the use of other quality males, thus narrowing the diversity of the gene pool.

The popular-sire syndrome is not limited to breeds with small populations. Some of the most populous breeds have had problems with this syndrome. Compounding this, there are several instances where a popular sire is replaced with a son, and even later a grandson. This creates a genetic bottleneck in the breeding population, narrowing the variety of genes available.

Every breed has its prominent dogs in the genetic background of the breed. But most of these dogs become influential based on several significant offspring that spread different combinations of the dog’s genes over several generations. The desirable and undesirable characteristics of the dog were passed on, expressed, evaluated by breeders, and determined if they were worthy of continuing in future generations.

The problem with the popularsire syndrome is that the dog’s genes are spread widely and quickly – without evaluation of the long-term effects of his genetic contribution.

The Challenges

The problem with the popular-sire syndrome is that the dog’s genes are spread widely and quickly – without evaluation of the long-term effects of his genetic contribution. By the time the dog’s genetic attributes can be evaluated through offspring and grandoffspring, his genes have already been distributed widely, and his effect on the gene pool may not be easily changed.

In almost all instances, popular sires are show dogs. They obviously have phenotypic qualities that are desirable, and as everyone sees these winning dogs, they are considered desirable mates for breeding. What breeders and especially stud-dog owners must consider is the effect of their mating selection on the gene pool. At what point does the cumulative genetic contribution of a stud dog outweigh its positive attributes? A popular sire may only produce a small proportion of the total number of litters registered. However, if the litters are all out of top-quality, winning bitches, then his influence and the loss of influence of other quality males may have a significant narrowing effect on the gene pool.

In some European countries, dog-breeding legislation is being considered that limits the lifetime number of litters a dog can sire or produce. If, however, certain matings produce only pet-quality dogs, but no quality breeding prospects, should the dog be restricted from siring a litter from a different line? The popular sire’s effect on the gene pool is on the number of offspring that are used for breeding in the next generation, and how extensively they are being used. This cannot be legislated.

At what point does a stud-dog owner determine that their dog has been bred enough? It can be difficult to deny stud service when asked, but the genetic effect of a dog on the whole breed must be considered. If everyone is breeding to a certain stud dog, the intelligent decision may be to wait and see what is produced from these matings. If you still desire what the stud dog produces, it is possible that you can find an offspring who has those positive attributes, and also a genetic contribution from its dam that you may find desirable. If a popular stud dog deserves to make a significant genetic contribution to the breed, doing so through multiple offspring, and therefore getting a mixed compliment of his genes, is better than focusing on a single offspring.

Wait-and-See Approach

All breeding dogs should be health tested for the conditions seen in the breed. If your breed has enrolled in the AKCCanine Health Foundation/Orthopedic Foundation for Animals CHIC program (, prospective breeding dogs and bitches should complete the recommended breedspecific health testing prior to breeding. These may include hip radiographs, CERF eye examinations, or specific genetic tests.

It is important to monitor the positive and negative characteristics being produced by popular sires. While it is satisfying to own a popular stud dog, a true measure of a breeder’s dedication is how negative health information in the offspring is made available. All dogs carry some undesirable traits. Based on the variety of pedigree background of bitches who are usually brought to popular sires, there is a greater chance that some undesirable traits could be expressed in the offspring. It is up to the stud-dog owner to keep in touch with bitch owners, and check on the characteristics that are being produced.

Some breeders will argue that the strength of a breed is in its bitches, but the fact remains that the stud dogs potentially have the greatest cumulative influence on the gene pool. There will always be popular sires, and that is not necessarily bad for a breed. But a dog’s influence on a breed should be gradual, and based on proven production and health testing. Maintaining surveillance of health and quality issues in breeding dogs and their offspring, and preserving the genetic diversity of the gene pool, should allow a sound future for purebred dogs.


Research: American dog breeds trace their ancestry to ancient Asia

Once thought to have been extinct, native American dogs are on the contrary thriving, according to a recent study that links these breeds to ancient Asia.

The arrival of Europeans in the Americas has generally been assumed to have led to the extinction of indigenous dog breeds; but a comprehensive genetic study has found that the original population of native American dogs has been almost completely preserved, says Peter Savolainen, a researcher in evolutionary genetics at KTH Royal Institute of Technology in Stockholm.

In fact, American dog breeds trace their ancestry to ancient Asia, Savolainen says. These native breeds have 30 percent or less modern replacement by European dogs, he says.

“Our results confirm that American dogs are a remaining part of the indigenous American culture, which underscores the importance of preserving these populations,” he says.

Savolainen’s research group, in cooperation with colleagues in Portugal, compared mitochondrial DNA from Asian and European dogs, ancient American archaeological samples, and American dog breeds, including Chihuahuas, Peruvian hairless dogs and Arctic sled dogs.

They traced the American dogs’ ancestry back to East Asian and Siberian dogs, and also found direct relations between ancient American dogs and modern breeds.

“It was especially exciting to find that the Mexican breed, Chihuahua, shared a DNA type uniquely with Mexican pre-Columbian samples,” he says. “This gives conclusive evidence for the Mexican ancestry of the Chihuahua.”

The team also analysed stray dogs, confirming them generally to be runaway European dogs; but in Mexico and Bolivia they identified populations with high proportions of indigenous ancestry.

Savolainen says that the data also suggests that the Carolina Dog, a stray dog population in the U.S., may have an indigenous American origin.