Humanized mice come down with hepatitis B and C

February 25, 2010 |12:04 | Genetics | Research  By : Team X


Yet another group of lab mice have been "humanized" so researchers can seek cures for infections that normally only strike people. Earlier this month, researchers at the University of North Carolina and Chapel Hill reported pre-exposure administration of a pair of anti-AIDS drugs help mice with humanized immune system warded off HIV infections.

Humanized mice come down with hepatitis B and C.

Researchers at the Salk Institute for Biological Studies have now announced they have created mice with livers full of human cells and then infected them with the B and C forms of hepatitis. Mice normally aren't susceptible to the viruses that cause these chronic liver ailments.

A team at Salk, in La Jolla, Calif., had previously generated a mouse with a partially "humanized" liver, but wanted to improve their method to achieve almost complete transformation. To that end, they used a special mouse that has liver problems of its own, but whose problems could be kept in check with a drug. Taking away the drug allows human liver cells, known as hepatocytes, to take hold within the mouse liver.

"We found that, not only can we infect our humanized mouse with Hepatitis B and Hepatitis C, but we can then successfully treat this infection using typical drugs," says Dr. Karl-Dimiter Bissig, an internist and post-doctoral researcher in the Salk Institute's Laboratory of Genetics. Normally, only humans and their fellow primates the chimpanzees are susceptible to Hepatitis B and C infections.

Bissig is the first author of a report on the researcher that was published Feb. 22 on the online edition of the Journal of Clinical Investigation.

The fact that biological threats such as viruses and bacteria usually only attack a narrow range of targets is known as host-pathogen specificity. This is why it is relatively rare for pathogens to jump between species, keeping disease from running wild.

On the other hand, it makes it harder to study the causes of and cures for human infectious diseases such as hepatitis or AIDS in mice and other lab animals. Studies involving human cells grown in lab dishes, known as cell cultures, often don't work.

"Human hepatocytes are almost impossible to work with as they don't grow and are hard to maintain in culture," says Inder Verma, a professor in the Laboratory of Genetics and holder of the Irwin and Joan Jacobs Chair in Exemplary Life Science. Verma is the study's senior author.

The Salk team reached a point at which 95 percent of the cells in the humanized, or chimeric, mice were human. They then discovered these mice could develop hepatitis B and C when infected with the viruses that cause them. Even better, they responded to pegylated interferon alpha 2a, an antiviral drug used to treat humans with hepatitis. Other experimental drugs were equally successful.

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