Rock2 heterozygosity improves recognition memory and endothelial function in a mouse model of 16p11.2 deletion autism...

Rho-associated protein kinase-2 (ROCK2) is a critical player in many cellular processes and was incriminated in cardiovascular and neurological disorders. Recent evidence has shown that non-selective pharmacological blockage of ROCKs ameliorates behavioral alterations in a mouse model of 16p11.2 haploinsufficiency. We had revealed that 16p11.2-deficient mice also display cerebrovascular abnormalities, including endothelial dysfunction. To investigate whether genetic blockage of ROCK2 also exerts beneficial effects on cognition and angiogenesis, we generated mice with both 16p11.2 and Rock2 haploinsufficiency (16p11.2^df/+;Rock2^+/-). We find that Rock2 heterozygosity on a 16p11.2^df/+ background significantly improved recognition memory. Furthermore, brain endothelial cells from 16p11.2^df/+;Rock2^+/- mice display improved angiogenic capacity compared to cells from 16p11.2^df/+ littermates. Overall, this study implicates Rock2 gene as a modulator of 16p11.2-associated alterations, highlighting its potential as a target for treatment of autism spectrum disorders.