Copper Toxicosis in Labrador Retrievers: Ongoing Research and Updated Information

The Labrador retriever community in the United States appears divided over the usefulness of a DNA test that identifies the ATP7B gene mutation that experts say makes Labs more susceptible to the deadly disease of copper toxicosis.  Some breeders use the test as just one tool to make breeding decisions while others don’t test and/or reject its validity.

Experts believe that there are other, undiscovered genetic mutations that also increase the risk for CT because some Labradors that developed the disease lacked the 7B gene mutation. Unfortunately, there apparently aren’t any American studies being conducted to find these other genetic mutations.

NEW DUTCH RESEARCH

However, Dutch researchers will soon release a study of the relationship among the 7B gene mutation, the ATP7A gene protectant mutation, and copper toxicosis (CT). They studied more than 400 Labradors, from whom liver biopsies and DNA were taken, “to better predict the value of the DNA test.”  A liver biopsy is the only way to know for certain if dogs have CT, experts say.

And there is more good news.

Dr. H. Fieten, one of the researchers, also says her group is “working on a biomarker in blood that can predict whether there is actual copper toxicosis present in an individual dog.”

She’s uncertain if the team’s effort “will be successful in developing a biomarker specific for copper (rather than hepatitis) but we are doing our best.” Dr. Fieten can’t predict if or when the marker will be developed.

In January 2016, Dutch researchers published their findings about their identification of the 7B gene mutation which they associated with an increased risk of CT in Labradors.  They also identified a 7A gene mutation which protects, to an unknown degree, Labradors from CT.

CT is an “inherited metabolic disease” affecting not only Labradors but other breeds and can result in liver failure, according to Casey Carl, DVM, of Paw Print Genetics (PPG) of Spokane, Washington. He says that dogs with this disease have a decreased ability to excrete dietary copper from the body, causing excessive copper storage in tissues and organs which can result in liver damage, cirrhosis and the inability of the liver to function properly.

Experts concur that the disease can kill both mixed breeds as well as purebreds. Besides Labradors, Bedlington Terriers and Dalmatians as well as possibly Doberman Pinchers and West Highland White Terriers are breeds with a known genetic makeup for the disease.

PPG is one of three American companies that offers a DNA test for the 7B and 7A gene mutations. Dr. Carl estimates that genetics account for only 42 percent of the overall risk for CT in Labradors. Fifty-eight percent is caused by non-inherited, environmental factors to include dietary intake of copper from food or water.

TESSA: SAVED BY ROUTINE BLOOD TEST 

Thanks to a routine blood test and an alert veterinarian, Tess, a champion agility Labrador, survived copper toxicosis in 2015.

Breeder/owner Angela Sutton’s vet in Redwood City, CA suspected copper toxicosis when she read the results of Tessa’s bloodwork. The dog’s liver biopsy came back positive for CT.

Tessa was treated with zinc acetate and put on a low copper raw diet as well as denamarin (a liver support supplement), Ursodiol (a bile acid) and Vitamin E. Tessa’s liver enzymes returned to normal a month later, so the zinc acetate was stopped, Sutton recalls. After about six months, Tessa returned to agility competitions.

When the DNA test for the CT gene mutations became available, Sutton tested her Labradors. Tessa tested clear for the 7B and 7A gene mutations as did Tessa’s litter sister and her dam, a Welsh import. Tessa’s sire had already died of unknown causes, at the age of ten, Sutton says.

Sadly, Tessa succumbed to an aggressive stomach cancer at the age of eleven years and two months. Sutton suspects that Tessa’s liver was compromised by CT and hurt the dog’s battle with cancer.

Both Tessa’s sister, at age eleven plus; and mother, at age seventeen plus; are doing well, Sutton says. As a precaution, she feeds them a low copper raw (Primal Raw Lamb) and organic cooked diet (sweet potato, broccoli, eggs, spinach, Greek yogurt as well as denamarin and Vitamin E. She uses a Canadian low copper kibble (Petcurian Go), primarily as training treats.

NIGHTMARE

“I never want to get another phone call like that,” says Darlene Pado of Seattle. She recalls her worst nightmare ― a puppy buyer who phoned for records while his puppy was being treated for liver failure at a veterinary hospital. The pup, just eight months old, died two weeks later in the summer of 2012. Pado learned that the pup had cirrhosis of the liver after her liver was biopsied.

Pado owned one of the pup’s littermates, Larson, and co-owned another, Margie, as well as their mother. She bred Larson in early 2016 and later learned that one of his daughters had gone into liver failure at seven months. The pup lived thanks to quick veterinary intervention and a low copper prescription diet, and later tested clear of the 7B gene mutation. Her owners declined to have a liver biopsy performed when she was later spayed.

By 2016, Pado knew about the existence of CT but the DNA test wasn’t available until the following year. She opted not to breed Larson again because she believed that both his deceased littermate and his daughter had CT. Her “experience and gut” told her that the CT was genetic and not environmentally caused.

In late 2016, she took a calculated risk when she bred Larson’s sister Margie, but only after fully disclosing that the canine possibly had a CT problem to the stud dog owner who assured her that she’d never experienced a CT issue in her line. Pado didn’t want to increase the risk of CT. She asked her puppy buyers to have a note placed in their dogs’ vet file about the possibility of CT in case the disease raised its ugly head.

Pado tested her dogs when the DNA test for the CT gene mutations became available. Larson and Margie each had one 7B and one 7A gene mutation. Their dam tested clear of the 7B gene mutation with two copies of the 7A (protective) gene mutation. Larson’s and Margie’s blood is tested annually to catch any issues, including elevated liver enzymes.

DNA TEST RESULTS

So far, a small percentage of this country’s Labrador population has been tested for the 7B and 7A gene mutations. As of December 2018, PPG had tested 1,208 Labradors. Vet Gen, a Michigan- based company, had tested 111 Labradors by the end of 2018. A third company, GenSol Diagnostics of Georgia, is just beginning to offer the test.

Only 2.32% of the Labradors tested by PPG had two copies of the 7B gene mutation, and almost 22% had one 7B gene mutation. PPG Medical Director Christina Ramirez reports that 76% had normal copies of 7B gene.

She also gives the following percentages based on the total number of Labradors tested. For females: 32.62% had two copies of the normal 7A gene, 26.66% had one normal and one mutation of the gene; and 5.96% had two copies of the 7A gene mutation. For males: 24.34% had a normal 7A gene and 10.43% had one 7A gene mutation. Only females can have two copies of this 7A gene and/or gene mutation.

Ramirez also says that more litters were tested in 2018 than in 2017.

VetGen reports that about 43% of the 111 tested Labradors (67 females, 43 males and one unknown) had one 7B gene mutation; and about 8% had two 7B gene mutations.  Fifty-four percent tested clear of the 7B gene mutation, and more than half of those dogs had at least one 7A gene mutation.

USE OF DNA TEST

Colorado breeder Lisa Butler, who bred Patron, an eleven-month-old puppy that died of CT but whose DNA was never tested thanks to lost samples, says she tests her dogs for the CT gene mutations before breeding them. (For more about Patron’s story, see https://www.caryunkelbach.com/copper-toxicosis-labrador-retrievers/ )

She believes that Labradors exhibiting CT symptoms are “few and far between compared to the number that have been tested and have the 7B gene mutation.” With this knowledge, she’s willing to gamble and breed a dog that has tested clear of the 7B gene mutation to a canine with one 7B gene mutation if it has all other health clearances and “something wonderful to offer.” She’ll avoid doubling up on the 7B gene mutation by not breeding dogs that carry that mutation to one another. (That’s what happened when Patron’s parents were bred to each other before both owners of the parents knew about the existence of CT.)

Butler says she might breed a dog clear of the 7B gene mutation to a dog that hadn’t been tested for the CT genes or to a dog with two 7B gene mutations if she knows that the dog hadn’t produced any symptomatic offspring. Although she doesn’t test entire litters for the CT 7B and 7A gene/gene mutations, she provides her puppy buyers with records of both parents’ health clearances to include CT DNA test results.

Pado thinks that her young dog Luna, a niece of the pup that died of what she believes to be CT in 2012, carries some risk of CT even though she was the only puppy in her litter that tested clear of the 7B gene mutation. Before she breeds her, she’ll not only carefully consider the health clearances of Luna and the potential stud dog but also their work ethic and conformation. She’ll use the CT DNA test as just one tool to make an informed decision and will ask breeders who she knows and trusts whether they know of any CT issues in the line of the potential stud dog. If so, she’ll look elsewhere. She plans to err on the side of caution.

Carrie Eberhardt, a self-described “science nerd” who breeds Labradors in the Dallas, Texas area, also uses the current DNA test as just one tool when making breeding decisions. She’s tested all her dogs, and come up with all 7B normal genes except for two that are now ten and fourteen-plus years. Those dogs each have one 7B and one 7A gene mutation but are going strong. She says that with a bit of luck, all her breeding-age females are clear of the 7B gene mutation and have at least one copy of the 7A gene mutation. She continues to test her Labradors and refuses to breed dogs that both have the 7B gene mutation to one another.

Eberhardt intends to breed one of her females to a stud dog with one 7B and one 7A gene mutation. She’ll not only educate her puppy buyers about CT but probably will also test the entire litter for CT and disclose those results to the new owners.

She also contacts her puppy buyers each year to check up on their dogs and carefully follows their wards’ health.

Eberhardt is all about more information and self-disclosure. Her dogs’ health test results are posted on her website and on a spreadsheet that lists the DNA test results for the 7B and 7A gene/gene mutations for Labradors, noting their sire and dam, in the files section of the Labrador Retrievers Copper Toxicosis Facebook private group page. (All of the breeders mentioned in this article post their dogs’ CT DNA results on this FB spreadsheet which currently lists about 160 Labradors.)

Some owners and breeders also disclose DNA test results at  www.pawprintspedigrees.com That site, however, lists disclosure of all health tests, not just for 7B and 7A gene test results.

Sutton advised the owners of Tessa’s relatives about Tessa’s CT diagnosis and the importance of routine bloodwork for early detection of CT. She later told them about the DNA CT test results for Tessa and her littermate as well as their mother, and that the test doesn’t identify all dogs at risk. “It was the right thing to do,” she says.

Cheri Wildes, an occasional breeder from Washington state, also practices full disclosure and education. She posts her dogs’ CT test results and lists CT clearances on her website. She not only talks to potential puppy buyers about CT but also provides information about the disease on her website.

She says that because she doesn’t breed a lot, “my primary goal is always to breed it (7B gene mutation) out in future generations to improve the line.” Her preference is to breed dogs that both carry the normal 7B gene and the 7A protectant gene mutation to one another. She’s bred 7B normal gene dogs to dogs with one 7B gene mutation but all carried at least one copy of the 7A gene mutation, and only after taking into consideration other health clearances and qualities. All of her dogs have at least one protectant (7A) gene mutation.

DIET INFORMATION

Although Wildes hasn’t personally experienced CT related issues, she understands that food may play a role in CT. She’s developed a spreadsheet for copper content of commercial dog food in the files section of the Copper Toxicosis in Labrador Retrievers FB page but believes the information needs to be monitored and updated at least every two years, and additional formulas of dog foods and more dog food brands should be added.

Wildes seeks volunteers to help with this time-consuming project and suggests obtaining information not only about copper content of the dog food but also zinc (known to reduce copper in food), calcium, and phosphorus. To help with this project, contact her at cheri@gunsuplabs.com

The American Association of Feed Control Officers doesn’t recommend maximum amount of copper in dog food, only minimum amounts which range from 7.3 mg/kg as a maintenance level for adults, and 12.4 mg/kg for pregnant/dams and puppies.

Dutch researchers have studied the effect of a low copper, high zinc diet in Labradors.  In one study, even though all but four dogs were clinically healthy, 75% had “an abnormally high hepatic copper concentration.” All the dogs ate commercially available dry kibble. The majority of the Labradors in this study were first-generation relatives of dogs affected CT and “thus might be at risk for inherited copper toxicosis.” https://www.onlinelibrary.wiley.com/doi/full/10.1111/j.1939-1676.2012.01001.x

Two additional studies conducted by Dutch researchers about low copper-high zinc content of dog food may be of interest to readers or their veterinarian: https://www.semanticscholar.org/paper/Dietary-Management-of-Labrador-Retrievers-with-Fieten-Biourge/675378df86f1a6ebd06fdd2fc979d6f770992bc2 and https://www.sciencedirect.com/science/article/pii/S1090023313006370

For additional information about dietary suggestions, research, and the experience of the Bedlington Terrier fanciers’ successful fight to control CT in their breed, see: https://www.caryunkelbach.com/copper-toxicosis-labrador-retrievers/

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