Pianp deficiency links GABA B receptor signaling and hippocampal and cerebellar neuronal cell composition to autism-like behavior

摘要: Pianp (also known as Leda-1) is a type I transmembrane protein with preferential expression in the mammalian CNS. Its processing characterized by proteolytic cleavage range of proteases including Adam10, Adam17, MMPs, and γ-secretase complex. can interact Pilrα GB1a subunit GABAB receptor (GBR) A recent case description boy global developmental delay homozygous nonsense variant PIANP supports hypothesis that involved control behavioral traits mammals. To investigate physiological functions Pianp, constitutive, knockout mice were generated comprehensively analyzed. Broad assessment did not indicate malformation or malfunction internal organs. In brain, however, decreased sizes altered cellular compositions dentate gyrus well cerebellum, lower number cerebellar Purkinje cells, identified. Functionally, loss led to impaired presynaptic GBR-mediated inhibition glutamate release gene cortex, hippocampus, amygdala, hypothalamus downregulation Erdr1, linked autism-like behavior. Behavioral phenotyping revealed deficiency leads context-dependent enhanced anxiety spatial learning deficits, an stress response, severely social interaction, repetitive behavior, which all represent characteristic features autism spectrum disorder-like phenotype. Altogether, represents novel candidate hippocampal pathology, GBR signaling.