Prss21-KO Mouse

Prss21, also known as testisin, is a gene encoding a glycosyl-phosphatidylinositol-linked serine protease. It is involved in multiple biological functions, including sperm cell maturation, angiogenesis regulation, and may play a role in tumor metastasis-related processes [1,2,3]. In the context of angiogenesis, it appears to regulate vascular integrity, and in sperm-related functions, it impacts sperm motility, morphology, and the ability to fertilize oocytes.

Genetic models, especially knockout mouse models, have been crucial in understanding Prss21 function. Prss21-deficient mice show increased vascular permeability and hemorrhagic phenotypes during luteal angiogenesis, suggesting its importance in maintaining vascular integrity [2]. In sperm-related studies, Prss21-deficient spermatozoa have decreased motility, abnormal tails, and impaired fertilizing ability, highlighting its role in epididymal sperm cell maturation [3]. Additionally, in ovarian cancer, increased testisin expression (from Prss21) inhibits intra-peritoneal tumor seeding, ascites accumulation, and metastatic tumor burden in a murine xenograft model [1].

In summary, Prss21 plays essential roles in sperm-related functions and angiogenesis, and its dysregulation may be associated with ovarian cancer metastasis. The use of KO mouse models has been instrumental in revealing these functions, providing valuable insights into potential therapeutic targets for treating infertility-related issues and ovarian cancer.

References:

1. Conway, Gregory D, Buzza, Marguerite S, Martin, Erik W, Pawar, Nisha R, Antalis, Toni M. 2019. PRSS21/testisin inhibits ovarian tumor metastasis and antagonizes proangiogenic angiopoietins ANG2 and ANGPTL4. In Journal of molecular medicine (Berlin, Germany), 97, 691-709. doi:10.1007/s00109-019-01763-3. https://pubmed.ncbi.nlm.nih.gov/30911775/

2. Peroutka, Raymond J, Buzza, Marguerite S, Mukhopadhyay, Subhradip, Driesbaugh, Kathryn H, Antalis, Toni M. 2020. Testisin/Prss21 deficiency causes increased vascular permeability and a hemorrhagic phenotype during luteal angiogenesis. In PloS one, 15, e0234407. doi:10.1371/journal.pone.0234407. https://pubmed.ncbi.nlm.nih.gov/32511276/

3. Netzel-Arnett, Sarah, Bugge, Thomas H, Hess, Rex A, Kay, Graham F, Antalis, Toni M. 2009. The glycosylphosphatidylinositol-anchored serine protease PRSS21 (testisin) imparts murine epididymal sperm cell maturation and fertilizing ability. In Biology of reproduction, 81, 921-32. doi:10.1095/biolreprod.109.076273. https://pubmed.ncbi.nlm.nih.gov/19571264/