Generation and Comparative Analysis of an Itga8-CreER Mouse with Preferential Activity in Vascular Smooth Muscle...

All current smooth muscle cell (SMC) Cre mice similarly recombine floxed alleles in vascular and visceral SMCs. Here, we present an Itga8-CreER knock-in mouse and compare its activity with a Myh11-CreER mouse. Both Cre drivers demonstrate equivalent recombination in vascular SMCs. However, Myh11-CreER mice, but not Itga8-CreER mice, display high activity in visceral SMC-containing tissues such as intestine, show early tamoxifen-independent activity, and produce high levels of CreER^T2 protein. Whereas Myh11-CreER -mediated knockout of serum response factor (Srf) causes a lethal intestinal phenotype precluding analysis of the vasculature, loss of Srf with Itga8-CreER (Srf ) yields viable mice with no evidence of intestinal pathology. Male and female Srf mice exhibit vascular contractile incompetence, and angiotensin II causes elevated blood pressure in wild type, but not Srf , male mice. These findings establish the Itga8-CreER mouse as an alternative to existing SMC Cre mice for unfettered phenotyping of vascular SMCs following selective gene loss.