Tmprss11a-KO Mouse

Tmprss11a, a member of the type II transmembrane serine protease (TTSP) family, has been implicated in multiple biological processes. It can cleave and activate spike proteins of coronaviruses like SARS-CoV, MERS-CoV, and SARS-CoV-2, as well as the influenza A virus hemagglutinin, potentially facilitating viral entry into target cells [2,3]. Additionally, it has been associated with cell migration, wound healing, and cellular senescence [1].

In terms of functional studies, in rodent and human skin and gingival samples, Tmprss11a levels increased with age. Overexpression of Tmprss11a decreased cell migration and spreading, and induced cellular senescence. It interacts with integrin β1 through an RGD sequence in its C-terminal domain, which is relevant for cell migration. ShRNA-mediated downregulation of Tmprss11a improved wound healing in the skin of old mice, but not in skeletal muscle where it is undetectable, indicating its tissue-specific role in wound healing [1]. Genetically modified mouse models, such as Tmprss11a-deficient mutant mouse strains, have been generated to explore its functions. These mice showed that Tmprss11a is dispensable for development, health, and long-term survival in the absence of external challenges or additional genetic deficits, suggesting a certain level of functional redundancy within the HAT/DESC subfamily of TTSPs to which it belongs [4].

In conclusion, Tmprss11a plays significant roles in viral infection, cell migration, and wound healing. The use of gene knockout (KO) mouse models has provided valuable insights into its functions, highlighting its dispensability under normal conditions yet importance in processes like wound healing and potential involvement in viral-related diseases [1,4].

References:

1. Fernandez, Christian, Burgos, Andres, Morales, Diego, Conboy, Irina M, Cáceres, Mónica. . TMPRSS11a is a novel age-altered, tissue specific regulator of migration and wound healing. In FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 35, e21597. doi:10.1096/fj.202002253RRR. https://pubmed.ncbi.nlm.nih.gov/33908663/

2. Zhang, Ce, Zhang, Yikai, Zhang, Shengnan, Dong, Ningzheng, Wu, Qingyu. 2020. Intracellular autoactivation of TMPRSS11A, an airway epithelial transmembrane serine protease. In The Journal of biological chemistry, 295, 12686-12696. doi:10.1074/jbc.RA120.014525. https://pubmed.ncbi.nlm.nih.gov/32675285/

3. Zmora, Pawel, Hoffmann, Markus, Kollmus, Heike, Schughart, Klaus, Pöhlmann, Stefan. 2018. TMPRSS11A activates the influenza A virus hemagglutinin and the MERS coronavirus spike protein and is insensitive against blockade by HAI-1. In The Journal of biological chemistry, 293, 13863-13873. doi:10.1074/jbc.RA118.001273. https://pubmed.ncbi.nlm.nih.gov/29976755/

4. Sales, Katiuchia Uzzun, Hobson, John P, Wagenaar-Miller, Rebecca, Molinolo, Alfredo A, Bugge, Thomas H. 2011. Expression and genetic loss of function analysis of the HAT/DESC cluster proteases TMPRSS11A and HAT. In PloS one, 6, e23261. doi:10.1371/journal.pone.0023261. https://pubmed.ncbi.nlm.nih.gov/21853097/