MUTATIONS IN THE MURINE FITNESS-1 GENE RESULT IN DEFECTIVE HEMATOPOIESIS

Identification and characterization of mutations that disrupt normal h ematopoiesis are essential for understanding the genetic pathways that control the development and regulation of the mammalian hematopoietic system. Previously, the fitness 7 gene was identified by five, indepe ndent mutations in N-ethyl-N-nitrosourea (ENU) saturation mutagenesis experiments within the albino (c) region of mouse chromosome 7 (MMU7), We report here that fit1 mutants are anemic, display numerous periphe ral blood defects, and are deficient in early hematopoietic progenitor cell populations, The number of both erythroid and myeloid progenitor s, as well as B cells, are reduced. These results implicate fit1 invol vement in normal hematopoiesis and suggest that further characterizati on of the fit1 gene, and the five presumed point mutations of the gene , will lead to an improved understanding of normal hematopoiesis in th e mouse. (C) 1997 by The American Society of Hematology.