Copper-induced hepatitis: the COMMD1 deficient dog as a translational animal model for human chronic hepatitis.
Chronic inflammatory liver disease regardless of aetiology leads to failing regeneration and fibrosis, ending in cirrhosis. Both in man and in animals this worldwide health problem has no definitive cure. Chronic liver injury causes hepatic stellate cells to proliferate and differentiate into matrix-producing cells. New therapeutic options will be developed upon detailed understanding of the molecular mechanisms driving liver fibrosis. This may lead to new anti-fibrotic therapies which need to be tested in suitable models before application in the veterinary and human clinic. On the other side, to restore the failing regenerative capacity of the diseased liver cells, adult progenitor cells are of interest, as an alternative to whole organ transplantation. In order to find the most suitable large animal model it is important to recognise that the typical histopathological reaction pattern of the liver can differ between mammalian species. It is therefore imperative that specialists in veterinary internal medicine and pathology, being familiar with the diseases and pathologies of the liver in different animal species, are teaming-up in finding the best models for veterinary and human liver diseases. Several large animal models have been mentioned, like pigs, sheep, and dogs. Based on the observations that man and dog share the same hepatopathies and have identical clinical, pathological and pathogenetic reaction patterns during the development of liver disease, the dog seems to be a properly suited species to test new therapeutic strategies for pets and their best friends.
Faculty of Veterinary Medicine, Department of Clinical Sciences of Companion Animals, Utrecht University, Utrecht, the Netherlands. r.p.favier@uu.nl
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Favier
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Spee
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Penning
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Rothuizen
D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency* / Q000235:genetics; D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000150:complications / Q000503:physiopathology*; D003300:Copper / Q000009:adverse effects* / Q000378:metabolism; D004195:Disease Models, Animal; D004283:Dog Diseases / Q000139:chemically induced / Q000235:genetics; D004285:Dogs; D006521:Hepatitis, Chronic / Q000150:complications; D006527:Hepatolenticular Degeneration / Q000150:complications; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications; D008115:Liver Regeneration; D051379:Mice; D018384:Oxidative Stress; D051381:Rats
D048868:Adaptor Proteins, Signal Transducing; D003300:Copper