DNA rearrangements located over 100 kb 5′ of the Steel (Sl)-coding region in Steel-panda and Steel-contrasted mice deregulate Sl expression and cause female sterility by disrupting ovarian follicle development

Mary A. Bedell, Camilynn I. Brannan, Edward P. Evans, Neal G. Copeland, Nancy A. Jenkins, Peter J. Donovan

Research output: Contribution to journalArticle

127 Scopus citations

Abstract

The Steel (Sl] locus is essential for the development of germ cells, hematopoietic cells, and melanocytes and encodes a growth factor (Mgf) that is the ligand for c-kit, a receptor tyrosine kinase encoded by the W locus. We have identified the molecular and germ cell defects in two mutant Sl alleles, Steel-panda (Slpan) and Steel-contrasted (Slcon), that cause sterility only in females. Unexpectedly, both mutant alleles are shown to contain DNA rearrangements, located >100 kb 5′ of Mgf-coding sequences, that lead to tissue-specific effects on Mgf mRNA expression. In Slpan embryos, decreased Mgf mRNA expression in the gonads causes a reduced number of primordial germ cells in both sexes. However, Mgf expression and spermatogenesis in the postnatal mutant testes is normal, and spermatogonial proliferation compensates for deficiencies in germ cell numbers. In SPpan and Slcon homozygous females, decreased Mgf mRNA expression causes sterility by affecting the initiation and maintenance of ovarian follicle development. Thus, regulated expression of Mgf is required for multiple stages of embryonic and postnatal germ cell development. Surprisingly, other areas of the Slcon female reproductive tract displayed ectopic expression of Mgf mRNA. We propose that the Slpan and Slcon rearrangements alter Mgf mRNA abundance through position effects on expression that act at a distance from the Sl gene.

Original languageEnglish (US)
Pages (from-to)455-470
Number of pages16
JournalGenes and Development
Volume9
Issue number4
DOIs
StatePublished - Feb 15 1995

Keywords

  • Female sterility
  • Gametogenesis
  • Ovarian follicle
  • Position effect mutation
  • Steel

ASJC Scopus subject areas

  • Developmental Biology
  • Genetics

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