A healthy future for Labradors

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The Labrador retriever is a beloved breed by many people. It is not surprising that their superfriendly character, joy, enthusiasm and working ethos steals the heart of many people. Labradors are not only beloved pets or hunting companions, because of their stable and gentle character they often fulfill a role as assistance or guide dog.

At the Centre of Expertise of Genetics of the Faculty of Veterinary Medicine, Utrecht University we work hard to keep the breed healthy by conducting genetic studies aiming to identify disease causing mutations in Labrador retrievers. By combining different research projects, more research output can be expected. Genetic studies require dogs that are affected by a certain disease, but also dogs that were free of disease and reached an old age in good health. By combining patient groups and groups of control dogs, we work efficiently towards solutions for hereditary diseases in the Labrador retrievers.

 

A better understanding of hereditary diseases 

 

The ultimate goal of the veterinary researchers of the Expertise Centre of Genetics  to unravel the genetic background of hereditary diseases in the Labrador retriever, which will lead to more effective diagnostics and therapeutics. Ultimately, the development of a diagnostic DNA-test can be implemented in breeding strategies for prevention of diseases in the Labrador retrievers.

In the current project, focused on Labrador retrievers, the research team aims to combine several research aspects for a leap forward in genetic research.

The diseases that are currently under investigation are:

 

Hereditary copper toxicosis

 

Copper toxicosis is a hereditary disease in Labrador retrievers, where copper that is taken up from diet and drinking water, cannot be effectively excreted and accumulates in the liver. This causes hepatitis and eventually liver cirrhosis. In approximately half of the Labrador retrievers that were admitted to our clinic, increased hepatic copper levels were identified.

When dogs are diagnosed in an early stage, treatment with a low copper / high zinc diet and copper chelation therapy, dog scan have a normal life expectancy in most cases. Unfortunately, every month we see Labrador retrievers for which diagnoses was too late for effective treatment. The research team previously identified genetic mutations that contribute to hepatic copper levels. In the current research project the team evaluates multiple mutations in a large group of Labrador retrievers for the development of a prediction model for copper toxicosis. They aim to develop a method for early diagnosis, so that effective treatment can be initiated in an early stage.

 

Ectopic ureters

 

Ectopic ureters is a congenital abnormality where ureters that transport urine from the kidney to the bladder, do not enter the bladder at an anatomical normal position. This is caused by an abnormal embryologic development, which can also lead to other abnormalities including absence of a kidney. The abnormal position of the ureters can lead to urinary incontinence and recurrent urinary tract infections. Recently, our researchers discovered in a small screening survey that one third of the investigated Labrador retrievers showed abnormal positioning of the ureters, without clinical symptoms. The results of this investigation are concerning, especially because these dogs did not show clinical signs and will go unnoticed and may be used for breeding. The current research project aims to identify genes that are responsible for ectopic ureters in the Labrador retriever. If you are an owner of a dog that has been diagnosed with ectopic ureters, you can contribute to the study by sending an EDTA blood sample to our research group. In that case, please contact us via ecgg@uu.nl.

 

Tricuspid valve dysplasia

 

Tricuspid valve dysplasia is an hereditary, congenital abnormality of the valve of the right hear. In pups a murmur can often be heard. Our advice is to always go with your pup to a cardiology specialist when a heart murmur is detected at heart auscultation. Tricuspid valve dysplasia may have a fatal course. It can lead to heart failure and accumulation of fluid in the abdomen, or to severe heart rhythm disturbances.  Besides financial support, we would need blood samples from Labradors affected with tricuspid valve disease. If your dog is diagnosed with tricuspid valve dysplasia and you want to contribute a blood sample from your dog, please contact us via ecgg@uu.nl.

 

Elbow dysplasia

 

Elbow dysplasia in the Labrador retriever is a severe problem, causing a lot of pain in dogs, that should be able to live a painful an playful life. Elbow dysplasia inevitably will lead to arthrosis of the elbow joint, and no good treatment is currently present. Our research team is searching for causal mutations leading to elbow dysplasia with the ultimate goal to develop a DNA-test that can be used for risk prediction in breeding strategies to effectively decrease the frequency of elbow dysplasia in the Labrador retriever population.  

  

Your support counts!

 

Please help us to ensure a healthy future for our Labrador retrievers. Your support will lead to better diagnostics, therapies of even the development of a DNA-test, all with the ultimate goal to obtain a healthy future for our beloved breed.

Together we can make a change!

 

 

List of publications of our previous studies in Labrador retrievers

 

 

Canine Copper-Associated Hepatitis.

Dirksen K, Fieten H.

Vet Clin North Am Small Anim Pract. 2017 May;47(3):631-644. doi: 10.1016/j.cvsm.2016.11.011.

 

Investigation of Genetic Modifiers of Copper Toxicosis in Labrador Retrievers.

Wu X, den Boer ER, Vos-Loohuis M, Steenbeek FGV, Monroe GR, Nijman IJ, Leegwater PAJ, Fieten H.

Life (Basel). 2020 Oct 31;10(11):266. doi: 10.3390/life10110266.

 

Quantification of the health-status of the Dutch Labrador retriever population.

Keijser SFA, Vernooij JCM, van Garderen E, van Rooijen P, Fieten H, van Steenbeek FG, Hesselink JW, Nielen M.

Prev Vet Med. 2019 Nov 1;171:104764. doi: 10.1016/j.prevetmed.2019.104764.

 

Evaluation of COMMD1 in copper toxicosis in Labrador retrievers and Dobermans.

Wu X, Mandigers PJJ, Fieten H, Leegwater PA.

Vet J. 2020 Nov;265:105561. doi: 10.1016/j.tvjl.2020.105561.

 

Association of circulating microRNA-122 and microRNA-29a with stage of fibrosis and progression of chronic hepatitis in Labrador Retrievers.

Sakai M, Spee B, Grinwis GCM, Penning LC, van Wolferen ME, van der Laan LJW, Fieten H.

J Vet Intern Med. 2019 Jan;33(1):151-157. doi: 10.1111/jvim.15366.

D-penicillamine treatment of copper-associated hepatitis in Labrador retrievers.

Fieten H, Dirksen K, van den Ingh TS, Winter EA, Watson AL, Leegwater PA, Rothuizen J.

Vet J. 2013 Jun;196(3):522-7. doi: 10.1016/j.tvjl.2012.12.013.

 

Dietary management of labrador retrievers with subclinical hepatic copper accumulation.

Fieten H, Biourge VC, Watson AL, Leegwater PA, van den Ingh TS, Rothuizen J.

J Vet Intern Med. 2015 May-Jun;29(3):822-7. doi: 10.1111/jvim.12574.

 

Sensitivity and Specificity of Plasma ALT, ALP, and Bile Acids for Hepatitis in Labrador Retrievers.

Dirksen K, Burgener IA, Rothuizen J, van den Ingh TSGAM, Penning LC, Spee B, Fieten H.

J Vet Intern Med. 2017 Jul;31(4):1017-1027. doi: 10.1111/jvim.14716.

 

Hepatocyte-derived microRNAs as sensitive serum biomarkers of hepatocellular injury in Labrador retrievers.

Dirksen K, Verzijl T, van den Ingh TS, Vernooij JC, van der Laan LJ, Burgener IA, Spee B, Fieten H.

Vet J. 2016 May;211:75-81. doi: 10.1016/j.tvjl.2016.01.010.

 

Nutritional management of inherited copper-associated hepatitis in the Labrador retriever.

Fieten H, Biourge VC, Watson AL, Leegwater PA, van den Ingh TS, Rothuizen J.

Vet J. 2014 Mar;199(3):429-33. doi: 10.1016/j.tvjl.2013.12.017.

 

Erythrocyte copper chaperone for superoxide dismutase and superoxide dismutase as biomarkers for hepatic copper concentrations in Labrador retrievers.

Dirksen K, Roelen YS, van Wolferen ME, Kruitwagen HS, Penning LC, Burgener IA, Spee B, Fieten H.

Vet J. 2016 Dec;218:1-6. doi: 10.1016/j.tvjl.2016.10.007.

 

The Menkes and Wilson disease genes counteract in copper toxicosis in Labrador retrievers: a new canine model for copper-metabolism disorders.

Fieten H, Gill Y, Martin AJ, Concilli M, Dirksen K, van Steenbeek FG, Spee B, van den Ingh TS, Martens EC, Festa P, Chesi G, van de Sluis B, Houwen RH, Watson AL, Aulchenko YS, Hodgkinson VL, Zhu S, Petris MJ, Polishchuk RS, Leegwater PA, Rothuizen J.

Dis Model Mech. 2016 Jan;9(1):25-38. doi: 10.1242/dmm.020263.

 

Association of dietary copper and zinc levels with hepatic copper and zinc concentration in Labrador Retrievers.

Fieten H, Hooijer-Nouwens BD, Biourge VC, Leegwater PA, Watson AL, van den Ingh TS, Rothuizen J.

J Vet Intern Med. 2012 Nov-Dec;26(6):1274-80. doi: 10.1111/j.1939-1676.2012.01001.

 

Heritabilities of copper-accumulating traits in Labrador retrievers.

Hoffmann G, Heuven HC, Leegwater PA, Jones PG, van den Ingh TS, Bode P, Rothuizen J.

Anim Genet. 2008 Aug;39(4):454. doi: 10.1111/j.1365-2052.2008.01722.x.

 

Prevalence and co-occurrence of hip dysplasia and elbow dysplasia in Dutch pure-bred dogs.

Lavrijsen IC, Heuven HC, Meij BP, Theyse LF, Nap RC, Leegwater PA, Hazewinkel HA.

Prev Vet Med. 2014 May 1;114(2):114-22. doi: 10.1016/j.prevetmed.2014.02.001.

 

Genome wide analysis indicates genes for basement membrane and cartilage matrix proteins as candidates for hip dysplasia in Labrador Retrievers.

Lavrijsen IC, Leegwater PA, Martin AJ, Harris SJ, Tryfonidou MA, Heuven HC, Hazewinkel HA.

PLoS One. 2014 Jan 30;9(1):e87735. doi: 10.1371/journal.pone.0087735.

 

Phenotypic and genetic evaluation of elbow dysplasia in Dutch Labrador Retrievers, Golden Retrievers, and Bernese Mountain dogs.

Lavrijsen IC, Heuven HC, Voorhout G, Meij BP, Theyse LF, Leegwater PA, Hazewinkel HA.

Vet J. 2012 Aug;193(2):486-92. doi: 10.1016/j.tvjl.2012.01.001.

 

Assessment of collagen genes involved in fragmented medial coronoid process development in Labrador Retrievers as determined by affected sibling-pair analysis.

Salg KG, Temwitchitr J, Imholz S, Hazewinkel HA, Leegwater PA.

Am J Vet Res. 2006 Oct;67(10):1713-8. doi: 10.2460/ajvr.67.10.1713.