Mouse Fem1b interacts with the Nkx3.1 homeoprotein and is required for proper male secondary sexual development.
Previous studies of epithelial cell growth and differentiation in the prostate gland have identified the homeodomain protein Nkx3.1 as a central regulator of prostate development and carcinogenesis. To understand the molecular mechanisms of Nkx3.1 function, we have used yeast two-hybrid analysis to identify Nkx3.1 interacting proteins, and have isolated Fem1b, a mammalian homolog of the C. elegans sex-determining gene Fem-1. In mice, the Fem1b and Nkx3.1 genes encode proteins that interact in glutathione-S-transferase (GST) pull-down and co-immunoprecipitation assays, and are co-expressed in the prostate and testis of neonatal mice. Null mutants for Fem1b generated by gene targeting display defects in prostate ductal morphogenesis and secretory protein expression, similar to phenotypes found in Nkx3.1 mutants. We propose that Fem1b may have a conserved role in the generation of sexual dimorphism through its interaction with Nkx3.1 in the developing prostate gland.
Wang
Xi
X
Center for Advanced Biotechnology and Medicine, Departments of Pediatrics, UMDNJ-Robert Wood Johnson Medical School, Piscataway, New Jersey, USA.
Desai
Nishita
N
Hu
Ya-Ping
YP
Price
Sandy M
SM
Abate-Shen
Cory
C
Shen
Michael M
MM
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D011485:Protein Binding; D046468:Sexual Development / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D043743:Ubiquitin-Protein Ligase Complexes; D014566:Urogenital System / Q000254:growth & development / Q000378:metabolism
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D018398:Homeodomain Proteins; C102837:Nkx3-1 protein, mouse; D014157:Transcription Factors; C498596:Fem1b protein, mouse; D043743:Ubiquitin-Protein Ligase Complexes