Shb null allele is inherited with a transmission ratio distortion and causes reduced viability in utero
Abstrakt
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 C57B16 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/C57B16/129Sv) 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.