• Hepsin, also known as TMPRSS1, is a Type II membrane protein with an extracellular serine protease domain. It is most highly expressed in liver, but is also present in many other tissues, notably lung, kidney, and skeletal muscle. A soluble form of Hepsin lacking the transmembrane domain has been identified. Hepsin is capable of activating Factor VII and may initiate blood coagulation at the cell surface. Hepsin is overexpressed in various human tumors, including prostate, and is considered to be a biomarker for prostate cancer.
• Mouse Hpn mRNA was only detectable in wild-type mice. Human HPN mRNA was exclusively detectable in homozygous B-hHPN mice but not in wild-type mice.
• The exons 4-14 of mouse Hpn gene that encode extracellular domain, transmembrane domain and 3’UTR region were replaced by human counterparts in B-hHPN mice. The genomic region of mouse Hpn gene that encode cytoplasmic portion was retained. The promoter and 5’UTR region of the mouse gene were also retained. The chimeric HPN expression was driven by endogenous mouse Hpn promoter, while mouse Hpn gene transcription and translation will be disrupted.

Gene targeting strategy for B-hHPN mice. The exons 4-14 of mouse Hpn gene that encode extracellular domain, transmembrane domain and 3’UTR region were replaced by human counterparts in B-hHPN mice. The genomic region of mouse Hpn gene that encode cytoplasmic portion was retained. The promoter and 5’UTR region of the mouse gene were also retained. The chimeric HPN expression was driven by endogenous mouse Hpn promoter, while mouse Hpn gene transcription and translation will be disrupted.

Strain specific analysis of HPN mRNA expression in wild-type C57BL/6 mice and B-hHPN mice by RT-PCR. Liver RNA were isolated from wild-type C57BL/6 mice (+/+) and homozygous B-hHPN mice (H/H), then cDNA libraries were synthesized by reverse transcription, followed by PCR with mouse or human HPN primers. Mouse Hpn mRNA was only detectable in wild-type mice. Human HPN mRNA was exclusively detectable in homozygous B-hHPN mice but not in wild-type mice.