Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adoptive Transfer
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Aging / immunology
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Albinism / genetics
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Alleles
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Animals
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B-Lymphocytes / pathology
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Bone Marrow Cells / pathology
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Colony-Forming Units Assay
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Erythropoiesis / genetics
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Female
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Graft Survival
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Hematopoiesis / genetics*
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Hematopoiesis / physiology
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Hematopoietic Stem Cells / chemistry
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Hematopoietic Stem Cells / pathology*
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Immunologic Deficiency Syndromes / genetics*
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Introns / genetics
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Male
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Mice, Mutant Strains
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Phenotype
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Point Mutation
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Protein Structure, Tertiary
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Proto-Oncogene Proteins c-kit / genetics*
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Proto-Oncogene Proteins c-kit / physiology
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RNA Splicing / genetics
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Radiation Chimera
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Specific Pathogen-Free Organisms
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Spleen / pathology
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Stem Cell Transplantation
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T-Lymphocytes / pathology
Substances
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Proto-Oncogene Proteins c-kit