Pms2 Conditional Knockout mouse models

As the endonuclease-bearing partner of MLH1 in the MutL alpha heterodimer, Pms2 (ortholog of human PMS2) executes the incision step of mismatch repair, using a conserved metal-binding endonuclease motif whose latent nickase activity is licensed by PCNA and RFC to introduce strand-discrimination nicks that direct EXO1 excision of the error-containing nascent strand. Biallelic germline loss causes constitutional mismatch repair deficiency with childhood brain tumors and hematologic malignancy, while monoallelic loss produces Lynch syndrome with microsatellite instability and a hypermutated, immunotherapy-responsive tumor genome. Null mice are viable but cancer prone and male infertile, so conditional alleles matter mainly for lineage-specific tumor initiation, whereas an endonuclease-dead knockin cleanly separates catalytic repair from the damage signaling and apoptotic functions of MutL alpha. Note that MLH1 also partners MLH3 and PMS1 in MutL gamma and MutL beta, so meiotic and somatic repair endpoints should not be treated as interchangeable.

Pms2 conditional knockout mice carry a floxed allele so you delete function only where Cre is active. The germline allele stays intact until you cross to a tissue specific Cre. Labs reach for this design when a global knockout is lethal, when they need adult onset loss, or when regional redundancy hides a whole body phenotype.