Viable c-KitW/W mutants reveal pivotal role for c-kit in the maintenance of lymphopoiesis

Mice lacking the receptor tyrosine kinase c-Kit (c-Kit(W/W)) have hematopoietic defects causing perinatal death. We have identified a viable c-Kit(W/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-Kit(W/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-Kit(W/W) strain, rescued by overexpression of erythropoietin.