Faculty Research 1990 - 1999

Developmental abnormalities in Steel17H mice result from a splicing defect in the steel factor cytoplasmic tail.

Document Type

Article

Publication Date

1992

Keywords

Animal, Base-Sequence, Blotting-Northern, Cytoplasm, DNA, Female, Fetal-Development: ge, Hematopoietic-Cell-Growth-Factors: ge, Homozygote, Male, Mice, Mice-Mutant-Strains, Molecular-Sequence-Data, Mutation, Plasmids, Proto-Oncogene-Proteins: ge, RNA-Splicing: ge, RNA-Messenger: ge, Sex-Differentiation: ge, SUPPORT-NON-U-S-GOVT, SUPPORT-U-S-GOVT-NON-P-H-S, SUPPORT-U-S-GOVT-P-H-S, Transfection

First Page

1832

Last Page

1842

JAX Source

Genes Dev 1992 Oct;6(10):1832-42

Grant

NOI-CO-74101/CO/NCI, HD20575/HD/NICHD

Abstract

The murine dominant White spotting (W) and Steel (Sl) loci encode the c-kit tyrosine kinase receptor and its cognate ligand steel factor (SLF), respectively. Mutations at either locus produce deficiencies in the same three migratory cell populations--those giving rise to pigment cells, germ cells, and blood cells. The identification of the gene products of these two loci combined with the plethora of W and Sl mutations available for molecular analysis offers a unique opportunity to dissect the role of a tyrosine kinase receptor and its cognate ligand during development in a fashion not possible for most other mammalian genes. Among the most interesting Sl mutations available for study are those that induce sterility in only one sex. In studies described here, we show that one of these alleles, Sl17H, which in the homozygous condition induces sterility in males but not females, is the result of a splicing defect in the SLF cytoplasmic tail. We also characterize the nature of the germ cell defects in male and female Sl17H mice and show that both sexes are affected equally during embryonic but not postnatal development. These studies provide new insights into the role of SLF in germ cell development and indicate that the cytoplasmic domain of SLF is important for its normal biological function.

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