Viable c-Kit(W/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.
D019264:Adoptive Transfer; D000375:Aging / Q000276:immunology; D000417:Albinism / Q000235:genetics; D000483:Alleles; D000818:Animals; D001402:B-Lymphocytes / Q000473:pathology; D001854:Bone Marrow Cells / Q000473:pathology; D003114:Colony-Forming Units Assay; D004920:Erythropoiesis / Q000235:genetics; D005260:Female; D006085:Graft Survival; D006410:Hematopoiesis / Q000235:genetics* / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000737:chemistry / Q000473:pathology*; D007153:Immunologic Deficiency Syndromes / Q000235:genetics*; D007438:Introns / Q000235:genetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D010641:Phenotype; D017354:Point Mutation; D017434:Protein Structure, Tertiary; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics* / Q000502:physiology; D012326:RNA Splicing / Q000235:genetics; D011828:Radiation Chimera; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000473:pathology; D033581:Stem Cell Transplantation; D013601:T-Lymphocytes / Q000473:pathology
D019009:Proto-Oncogene Proteins c-kit