Sci. STKE, 1 August 2000
Immunology Mice and Men are STATistically Different
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-α and IFN-β) 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]
Citation: Mice and Men are STATistically Different. Sci. STKE 2000, tw10 (2000).
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