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© The Rockefeller University Press, 0022-1007/1998/2/571/ $5.00
The Journal of Experimental Medicine, Volume 187, Number 4, February 16, 1998 571-578


Articles

The Orphan Receptor CRF2-4 Is an Essential Subunit of the Interleukin 10 Receptor

Susan D. Spencer*, Francesco Di Marco{ddagger}, Jeff Hooley*, Sharon Pitts-Meek*, Michele Bauer*, Anne M. Ryan*, Bernard Sordat{ddagger}, Verna C. Gibbs§, and Michel Aguet{ddagger}

From the * Genentech Inc., South San Francisco, California 94080; the {ddagger} 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

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.


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: michel.aguet{at}isrec.unil.ch

1 Abbreviations used in this paper: CRF2, class II cytokine receptor family; ES, embryonic stem; LIF, leukemia inhibitory factor; TF, tissue factor.


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