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.
The Orphan Receptor CRF2-4 Is an Essential Subunit of the Interleukin 10 Receptor
We thank Kelly Hagler, Laurie Leong, Lorena Cabote, Julio Ramirez, Fatima da Conceicao-Silva for histopathologic and hematologic examinations, and Dr. R.D. Schreiber for advice and suggestions.
Part of this work was supported by National Institutes of Health grant R29 DK-48748 (to V.C. Gibbs).
Address correspondence to Michel Aguet, Swiss Institute for Experimental Cancer Research (ISREC), 155, Ch. des Boveresses, 1066 Epalinges s/Lausanne, Switzerland. Phone: 41-21-692-5918; Fax: 41-21-652-6933; E-mail: [email protected]
Abbreviations used in this paper: CRF2, class II cytokine receptor family; ES, embryonic stem; LIF, leukemia inhibitory factor; TF, tissue factor.
Susan D. Spencer, Francesco Di Marco, Jeff Hooley, Sharon Pitts-Meek, Michele Bauer, Anne M. Ryan, Bernard Sordat, Verna C. Gibbs, Michel Aguet; The Orphan Receptor CRF2-4 Is an Essential Subunit of the Interleukin 10 Receptor . J Exp Med 16 February 1998; 187 (4): 571–578. doi: https://doi.org/10.1084/jem.187.4.571
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