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New chimeric mouse model for human liver diseases, drug testing
Date:12/4/2007

red if only five percent of all hepatocytes would express the missing enzyme, he says.

In fact, thats the underlying principle of the Salk researchers new chimeric mouse. It is based on a murine model for hereditary tyrosinaemia type I, developed by researchers at Oregon Healthy & Science University. An enzymatic defect in the tyrosine catabolism results in a toxic accumulation of byproducts within hepatocytes unless the mice are treated with a drug called NBTC.

Withdrawing the drug allows to selectively expand hepatocytes that do not have this defect, such as transplanted human hepatocytes. Within three months of transplantation, up to 20 percent of the mouse liver is repopulated by human hepatocytes. But whats more, the transplanted cells keep producing a foreign protein slipped inside with the help of a lentiviral vector, the kind usually used for gene therapy. We are very excited about that aspect since very often cells shut off the production of proteins introduced as part of gene therapy, says Verma.


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Contact: Gina Kirchweger
kirchweger@salk.edu
858-453-4100 x1340
Salk Institute  
Source:Eurekalert

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