Identifying Novel Roles for Peptidergic Signaling in Mice

PamcKO/cKO mice, with loxp sites flanking exons previously deleted in the global Pam knockout, were created, viable and equivalent to wildtype mice in every test. Eliminating Pam expression in excitatory forebrain neurons reduced anxiety-like behavior, increased locomotor responsiveness to cocaine and improved thermoregulation in the cold. Eliminating Pam expression in cardiomyocytes increased anxiety-like behavior, improved thermoregulation and markedly diminished atrial levels of pro-atrial natriuretic peptide. RNASeq analysis of atria revealed a set of PAM-regulated transcripts related to cardiac function. Examination of mRNA profiles in mouse atria expressing basal or reduced levels of PAM, followed by biochemical, behavioral and physiological analyses.