Shb null allele is inherited with a transmission ratio distortion and causes reduced viability in utero.
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.
Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden.
Vitezslav
V
Kriz
Jaroslav
J
Mares
Parri
P
Wentzel
Nina S
NS
Funa
Gabriela
G
Calounova
Xiao-Qun
XQ
Zhang
Karin
K
Forsberg-Nilsson
Maud
M
Forsberg
Michael
M
Welsh
D000015:Abnormalities, Multiple / Q000235:genetics; D000483:Alleles; D000818:Animals; D001755:Blastocyst / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006579:Heterozygote; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008957:Models, Genetic; D010060:Ovulation; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000502:physiology*
D011518:Proto-Oncogene Proteins; C085634:Shb protein, mouse