IMMUNOLOGY Mice and Men are STATistically Different

Abstract:

Despite the use of mice as an experimental model for human disease, there are several differences that prevent the extrapolation of mouse data to humans. Type 1 interferons (IFN- and IFN-ß) do not elicit STAT4 activation nor do they promote T helper cell type 1 (Th1) development in mice. However, in humans, type 1 interferons are important for STAT4 activation and Th1 cell development. Farrar et al. untie this immunological Gordian knot by determining that murine Stat2 contains a repetitive satellite insertion that substantially changes the 3' coding region. Thus, the COOH-terminal sequence of murine STAT2 is quite different from that of human STAT2. Expression studies revealed that STAT2 is required for STAT4 activation, and in humans, the COOH-terminus of STAT2 is critical for STAT4 activation. By using a chimeric protein consisting of the mouse NH₂-terminal region and the human COOH-terminal region of STAT2, the authors showed that the human COOH-terminus restored the capacity of STAT2 to activate STAT4.

Farrar, J.D., Smith, J.D., Murphy, T.L., Leung, S., Stark, G.R., and Murphy, K.M. (2000) Selective loss of type I interferon-induced STAT4 activation caused by a minisatellite insertion in mouse Stat2. Nature Immunol. 1: 65-69. [Online Journal]