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J. Exp. Med.,
Volume 187, Number 4, February 16, 1998 571-578
By



From the * Genentech Inc., South San Francisco, California 94080; the The orphan receptor CRF2-4 is a member of the class II cytokine receptor family (CRF2),
which includes the interferon receptors, the interleukin (IL) 10 receptor, and tissue factor.
CRFB4, the gene encoding CRF2-4, is located within a gene cluster on human chromosome
21 that comprises three interferon receptor subunits. To elucidate the role of CRF2-4, we disrupted the CRFB4 gene in mice by means of homologous recombination. Mice lacking
CRF2-4 show no overt abnormalities, grow normally, and are fertile. CRF2-4 deficient cells
are normally responsive to type I and type II interferons, but lack responsiveness to IL-10. By
~12 wk of age, the majority of mutant mice raised in a conventional facility developed a
chronic colitis and splenomegaly. Thus, CRFB4 mutant mice recapitulate the phenotype of
IL-10-deficient mice. These findings suggest that CRF2-4 is essential for IL-10-mediated effects and is a subunit of the IL-10 receptor.
Swiss Institute for Experimental
Cancer Research, 1066 Epalinges s/Lausanne, Switzerland; and the § Department of Surgery, San
Francisco Veterans Affairs Medical Center, San Francisco, California 94121
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