Immunity
Volume 17, Issue 3, September 2002, Pages 277-288
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Article
Viable c-KitW/W Mutants Reveal Pivotal Role for c-Kit in the Maintenance of Lymphopoiesis

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Abstract

Mice lacking the receptor tyrosine kinase c-Kit (c-KitW/W) have hematopoietic defects causing perinatal death. We have identified a viable c-KitW/W mouse, termed the “Vickid” mouse. Around birth, c-Kit plays a redundant role in T and no role in B cell development. Here, we show an age-dependent, progressive decline of pro-T and pro-B cells accompanied by loss of common lymphoid progenitors in the bone marrow in adult mice lacking c-Kit. Adult c-KitW/W hematopoietic stem cells can engraft in host bone marrow but fail to radioprotect, form spleen colonies, or establish sustained lymphopoiesis. These defects in adult T and B cell development are also evident in a second viable c-KitW/W strain, rescued by overexpression of erythropoietin.

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Present address: Pharmacenter, University of Basel, CH-4056 Basel, Switzerland.

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Correspondence: Claudia Waskow, 49-731-5002-3368 (phone), 49-731-5002-3367 (fax); e-mail: [email protected]