Null mutation of the transcription factor inhibitor of DNA binding 3 (ID3) in male mice adversely impacts on fertility and reproductive outcome.
Inhibitor of DNA binding 3 (ID3) protein binds to and inhibits the function  of basic helix-loop-helix transcription factors. The expression of ID3 protein  in postproliferative Sertoli cells in the testis, as well as its unique,  highly region-specific expression profile along the adult epididymis, implies  novel functional roles for this regulator of transcription. The purpose of  this study was to determine the effect of Id3 deficiency on male  fertility and progeny outcome. We observed that fertility status of  Id3(-/-) males is adversely affected. Males  having this null mutation did not sire any litters when crossed with wild-type  C57Bl/6 females; although pregnancies were induced in these females, these  never resulted in the birth of live pups. Additionally, abnormal reproductive  outcomes and developmental phenotypes were observed in gestational day 18  fetuses resulting from crosses with an Id3-deficient sire and  wild-type CD-1 females; these were characterized by an elevated rate of fetal  death, reduced body weights of live fetuses, a higher rate of external  malformations, and aberrant skeletal development. Importantly, we observed  that mutation of this gene differentially affects the phenotype of resulting  offspring, depending on the genotype of the parent, not necessarily the  genotype of the fetus itself. These results provide novel insight into the  role of Id3, suggesting that Id3 might coordinate gene  expression programs in the male reproductive system associated with the  generation of healthy offspring.
Department of Pharmacology and Therapeutics, McGill University, 3655 Promenade Sir-William-Osler, Rm 104, Montréal, Québec, Canada.
Michelle
M
Carroll
Bernard
B
Robaire
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D005260:Female; D005298:Fertility / Q000235:genetics*; D047109:Fetal Development / Q000235:genetics; D051796:Inhibitor of Differentiation Proteins / Q000172:deficiency / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D011247:Pregnancy; D011256:Pregnancy Outcome; D012098:Reproduction / Q000235:genetics*
D051792:Basic Helix-Loop-Helix Proteins; D051796:Inhibitor of Differentiation Proteins; C067679:Idb3 protein, mouse