Plat Knockout mouse models

Plat is the mouse ortholog of human PLAT and encodes tissue-type plasminogen activator, a serine protease built from finger, EGF, two kringle, and catalytic domains that cleaves plasminogen at the Arg-Val activation bond, with fibrin acting as a template that accelerates catalysis several hundred fold. Activity is restrained by PAI-1 (Serpine1) and neuroserpin, circulating enzyme is cleared through LRP1, and in brain tPA additionally processes proBDNF and the NMDA receptor NR1 subunit, linking it to excitotoxicity and barrier opening. Because nulls are viable with only mild fibrin persistence, informative designs combine conditional deletion (endothelial, hepatocyte, or neuronal) with a thrombotic or injury challenge, whereas catalytically dead knockins separate proteolysis from receptor-mediated actions. Plau provides substantial redundancy, so compound Plat Plau animals are needed to expose the full fibrinolytic deficit, and allele class should track the endpoint, whether clot lysis, wound repair, or infarct volume.

Whole body loss of Plat gives the clearest readout when the question is whether the gene is required at all. Follow up tissue work can still move to a conditional allele if lethality or compensation appears.