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Keywords:

  • SHB;
  • knockout;
  • ovulation;
  • malformations;
  • viability in utero;
  • transmission ratio distortion

Abstract

SHB is an Src homology 2 domain-containing adapter protein that has been found to be involved in numerous cellular responses. We have generated an Shb knockout mouse. No Shb−/− pups or embryos were obtained on the C57Bl6 background, indicating an early defect as a consequence of Shb- gene inactivation on this genetic background. Breeding heterozygotes for Shb gene inactivation (Shb+/−) on a mixed genetic background (FVB/C57Bl6/129Sv) reveals a distorted transmission ratio of the null allele with reduced numbers of Shb+/+ and Shb−/− animals, but increased number of Shb+/− animals. The Shb allele is associated with various forms of malformations, explaining the relative reduction in the number of Shb−/− offspring. Shb−/− animals that were born were viable, fertile, and showed no obvious defects. However, Shb+/− female mice ovulated preferentially Shb oocytes explaining the reduced frequency of Shb+/+ mice. Our study suggests a role of SHB during reproduction and development. Developmental Dynamics 236:2485–2492, 2007. © 2007 Wiley-Liss, Inc.