Impaired amygdala-based learning and decreased anxiety in a murine model of pseudohypoparathyroidism type 1A.

Pseudohypoparathyroidism type 1A (PHP1A) is a genetic disorder caused by maternally inherited mutations in the gene Gnas. PHP1A is characterized by multiple hormone impairment, early onset obesity and cognitive impairment. Animal models of PHP1A are needed to investigate the mechanism of cognitive impairment. In the present study we used the cre-lox murine model to investigate behavior and cognition in maternally vs. paternally inherited gnas mutations expressed in the central nervous system. We observed a behavioral phenotype of decreased anxiety and impaired amygdala-based learning in the PHP1A mutant mouse model though there was no difference in hippocampal based learning tasks. In the elevated zero maze and open field analysis in the locomotor activity chambers, mutant mice showed diminished anxiety/increased impulsivity which could correlate with the attention deficit phenotype of children with PHP1A. The mutant mice also demonstrated poorer motor strength on the inverted screen test. These findings mirror some clinical features of PHP1A though overall the murine phenotype was milder than expected.