title: Phenotypic analysis of mice lacking the Tmprss2-encoded protease.
abstract: Tmprss2 encodes an androgen-regulated type II transmembrane serine protease (TTSP) expressed highly in normal prostate epithelium and has been implicated in prostate carcinogenesis. Although in vitro studies suggest protease-activated receptor 2 may be a substrate for TMPRSS2, the in vivo biological activities of TMPRSS2 remain unknown. We generated Tmprss2-/- mice by disrupting the serine protease domain through homologous recombination. Compared to wild-type littermates, Tmprss2-/- mice developed normally, survived to adulthood with no differences in protein levels of prostatic secretions, and exhibited no discernible abnormalities in organ histology or function. Loss of TMPRSS2 serine protease activity did not influence fertility, reduce survival, result in prostate hyperplasia or carcinoma, or alter prostatic luminal epithelial cell regrowth following castration and androgen replacement. Lack of an observable phenotype in Tmprss2-/- mice was not due to transcriptional compensation by closely related Tmprss2 homologs. We conclude that the lack of a discernible phenotype in Tmprss2-/- mice suggests functional redundancy involving one or more of the type II transmembrane serine protease family members or other serine proteases. Alternatively, TMPRSS2 may contribute a specialized but nonvital function that is apparent only in the context of stress, disease, or other systemic perturbation.
authors.affiliation: Division of Human Biology, Fred Hutchinson Cancer Research Center, Mailstop D4-100, 1100 Fairview Avenue North, Seattle, WA 98109-1024, USA.
authors.forename: Tom S
authors.initials: TS
authors.lastname: Kim
authors.forename: Cynthia
authors.initials: C
authors.lastname: Heinlein
authors.forename: Robert C
authors.initials: RC
authors.lastname: Hackman
authors.forename: Peter S
authors.initials: PS
authors.lastname: Nelson
mesh_terms: D000818:Animals; D004848:Epithelium / Q000187:drug effects / Q000502:physiology; D005260:Female; D005298:Fertility / Q000235:genetics; D008297:Male; D051379:Mice; D010641:Phenotype; D011467:Prostate / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D021381:Protein Transport / Q000235:genetics; D044462:Receptors, Proteinase-Activated / Q000235:genetics / Q000378:metabolism*; D012038:Regeneration / Q000235:genetics; D012669:Seminal Vesicles / Q000378:metabolism; D017384:Sequence Deletion; D012697:Serine Endopeptidases / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D013739:Testosterone / Q000494:pharmacology; D014018:Tissue Distribution
chemical_list: D044462:Receptors, Proteinase-Activated; D013739:Testosterone; D012697:Serine Endopeptidases; C421305:TMPRSS2 protein, human