The orphan receptor CRF2-4 is an essential subunit of the interleukin 10 receptor

SD Spencer, F Di Marco, J Hooley… - The Journal of …, 1998 - rupress.org
SD Spencer, F Di Marco, J Hooley, S Pitts-Meek, M Bauer, AM Ryan, B Sordat, VC Gibbs…
The Journal of experimental medicine, 1998rupress.org
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 …
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.
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