• PERP, also known as PIGPC1 and THW, is a four-stage transmembrane protein. p53 binds to PERP promoter to transcribe and activate PERP gene, and the translated PERP protein mediates p53-induced apoptosis. In the development of many tumors, PERP expression is down-regulated, leading to reduced apoptosis of cancer cells and decreased adhesion, promoting cancer cell invasion and metastasis. Therefore, restoring PERP gene expression in cancer tissues could be a potential means of cancer treatment.
• Down-regulation of PERP is a common feature of many cancers, and PERP humanized mice can be used to evaluate the efficacy and safety of these tumor models.

Gene targeting strategy for B-hPERP mice. The exons 1-3 of mouse Perp gene that encode the whole molecule (ATG to STOP codon), including 3’UTR were replaced by human counterparts in B-hPERP mice. The promoter and 5’UTR region of the mouse gene are retained. The human PERP expression is driven by endogenous mouse Perp promoter, while mouse Perp gene transcription and translation will be disrupted. 

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

Western blot analysis of PERP protein expression in homozygous B-hPERP mice. Various tissue lysates were collected from wild-type C57BL/6JNifdc mice (+/+) and homozygous B-hPERP mice (H/H), and then analyzed by western blot with anti-PERP antibody(abcam, ab129083). 40 μg total proteins were loaded for western blotting analysis. PERP was detected in skin, heart, liver and lung of humanized mice.