Transgenic Mice Aid Research Into Deadly Cancer

Previous attempts to engineer such "Burkitt's mice" failed, but a team of scientists at the National Institutes of Health (NIH) finally came up with the right genetic mix. "We in effect created a 'mini-gene' that reproduces the cancer as it occurs in people," says Herbert C. Morse III, M.D., chief of the immunopathology lab at the National Institute of Allergy and Infectious Diseases (NIAID). The results of this work, supported by NIAID and the National Cancer Institute (NCI), are detailed in the current issue of the Journal of Experimental Medicine.

"This new animal model may allow researchers to find ways to treat Burkitt's patients who don't respond to the standard treatment," says Dr. Morse. "It will also help us understand why the cells 'go bad' to cause this malignancy." Scientists still don't know all the factors that contribute to Burkitt's lymphoma in people, despite having created Burkitt's mice.

Scientists do know that Burkitt's lymphoma arises in the immune system, and that the groundwork for the cancer is laid when a gene called MYC (pronounced "mick") is accidentally moved from its usual spot on chromosome 8 to a new location, often on chromosome 14. Normally, the MYC gene, which stimulates cell growth, is strictly controlled by nearby regulator genes on chromosome 8. But when MYC slips away to a different chromosome, it also evades its controls. Under the looser supervision of regulatory genes that govern the immune system, MYC "goes ripping out of control," Dr. Morse explains, causing runaway growth of the immune system's B cells, which in turn leads to tumors called lymphomas.

But scientists have much more to learn about how other genetic mutations, environmental factors and infectious agents, such as the Epstein-Barr virus, work together to cause Burkitt's lymphoma. In fact, studying the Burkitt's mice may lead to new understandings about why some people are predisposed to Burkitt's lymphoma, while other people are predisposed to other kinds of cancers, says Siegfried Janz, M.D., of NCI. "The only way to find this out is to invest basic research into mouse models of cancer," he argues. Clinicians might also use such a mouse model to test new treatments, he adds.

Achieving a Burkitt's mouse would not have been possible without previous work done by other NIAID scientists, Morse notes, particularly Janet Hartley, Ph.D., and Torgny Frederickson, Ph.D., who have spent years examining lymphomas in mice. The success also owes much to collaborator George Bornkamm, M.D., and his team at the Institute for Clinical Molecular Biology and Tumor Genetics in Munich, Germany.

Burkitt's lymphoma was first identified in 1958 by Denis Parsons Burkitt, an English surgeon in Africa who noticed it among the children there. The disease accounts for over half of all childhood cancers in Africa, where it affects about two out of 100,000 children every year. Incidence in Western countries is much lower, but has been on the rise with the spread of AIDS, since the cancer also strikes adults with compromised immune systems.

NIAID is a component of the NIH. NIAID supports basic and applied research to prevent, diagnose, and treat infectious and immune-mediated illnesses, including HIV/AIDS and other sexually transmitted diseases, tuberculosis, malaria, autoimmune disorders, asthma and allergies.

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Reference:S Janz, HC Morse III, et al. Burkitt's lymphoma in the mouse. Journal of Experimental Medicine 92(8):1183-90 (2000).

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