Effects of spontaneous KitlSteel mutations on survival and red blood cells of mice

Kit ligand (Kitl), which is a member of the helical cytokine superfamily, is encoded by the Steel (Sl) locus of mice and is essential for the development of hematopoietic cells, germ cells, and melanocytes. A large series of Kitl(Sl) alleles has been described, including some that arose spontaneously and others that were induced by either chemical or radiation mutagenesis. Here we describe the nucleotide sequence alterations in two spontaneous Kitl(Sl) alleles. The Kitl(Sl-18R) allele has a point mutation that introduces a premature termination codon, and the encoded protein is expected to be null functionally. The Kitl(Sl-5R) allele has an in-frame deletion that results in deletion of amino acids at position 31 and 32 of Kitl. While both mutations exert severe effects on blood cells and survival of homozygous mice, these effects are slightly milder than those of a previously characterized spontaneous deletion allele, Kitl(Sl-gb). Examination of the survival of compound heterozygotes provided strong genetic evidence that the Kitl(Sl-18R) and Kitl(Sl-5R) mutants are null functionally for mouse survival.