The Salk team had previously generated a mouse with a partially "humanized" liver, but wanted to improve their method to achieve almost complete transformation. They use a special mouse that has liver problems of its own, but whose problems can be kept in check with a drug called NBTC. Taking away NBTC allows human hepatocytes to take hold and populate the mouse liver with human cells.

The team perfected this system so that nearly 95% of the liver cells are of human origin, but the important question was whether they would behave like a human livers. To test this, the researchers exposed the mice to Hepatitis B and Hepatitis C and found that, unlike normal mice, which are resistant to these viruses, the chimeric animals developed the disease.

More importantly, using pegylated interferon alpha 2a-the standard treatment for Hepatitis C-the researchers showed that the "humanized" liver inside the mouse responds just like a normal human liver. The team also tested additional experimental drugs and found that they too behaved as they did in humans.

"This shows that our chimeric mouse model is medically relevant and can be used to validate novel drugs in a pre-clinical setting," says Bissig. "This is great news as it provides us with a tool with which we can examine many human hepatotropic pathogens, including malaria. In the future, it also has potential applications for regenerative medicine; allowing confirmation of the true hepatocyte nature of cells prior to human transplantation."

The methodology of generating these mice is freely available to the research community.

Source: Salk Institute for Biological Studies: