Related Experiment Video
Updated: Aug 13, 2026
A Phenotyping Regimen for Genetically Modified Mice Used to Study Genes Implicated in Human Diseases of Aging
Published on: July 14, 2016
Phenotypic analysis of mice lacking the Tmprss2-encoded protease
Tom S Kim1, Cynthia Heinlein, Robert C Hackman
1Division of Human Biology, Fred Hutchinson Cancer Research Center, Mailstop D4-100, 1100 Fairview Avenue North, Seattle, WA 98109-1024, USA.
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.
Insights
Mice lacking the TMPRSS2 gene showed no health issues or prostate abnormalities. This suggests other serine proteases may compensate for TMPRSS2's function in vivo.
Area of Science:
- Biochemistry
- Genetics
- Molecular Biology
Background:
- TMPRSS2 (Transmembrane protease, serine 2) is an androgen-regulated enzyme crucial in prostate epithelium.
- Its role in prostate carcinogenesis is suspected, but in vivo functions remain largely unknown.
- Protease-activated receptor 2 is a potential substrate, but biological activity requires in vivo validation.
Purpose of the Study:
- To investigate the in vivo biological functions of TMPRSS2.
- To determine the necessity of TMPRSS2's serine protease activity for normal prostate function and development.
- To assess the impact of TMPRSS2 deficiency on prostate carcinogenesis and fertility.
Main Methods:
- Generation of Tmprss2-/- mice via homologous recombination, targeting the serine protease domain.
- Phenotypic analysis of knockout mice, including survival, fertility, prostatic secretion analysis, organ histology, and cell regrowth post-castration.
- Assessment of transcriptional compensation by related Tmprss2 homologs.
Main Results:
- Tmprss2-/- mice exhibited normal development, survival, and fertility compared to wild-type littermates.
- No discernible abnormalities in prostate histology, function, or luminal epithelial cell regrowth were observed.
- Prostatic secretion protein levels remained unchanged, and no increased incidence of hyperplasia or carcinoma was noted.
- Transcriptional compensation by homologous genes was ruled out as a cause for the lack of phenotype.
Conclusions:
- The absence of a phenotype in Tmprss2-/- mice suggests functional redundancy within the serine protease family.
- TMPRSS2 may perform specialized, non-essential functions revealed only under specific stress or disease conditions.
- Further research is needed to elucidate the precise role of TMPRSS2 in prostate health and disease.
