Bazedoxifene reverses sexually dimorphic autistic-like abnormalities in biallelic MDGA1-mutant mice

ABSTRACT: MDGA1 reportedly suppresses GABAergic synaptic inhibition and may be associated with schizophrenia. However, it has been unclear whether and how MDGA1 dysfunction causes neurodevelopmental disorders. Here, we describe two patients with autism spectrum disorder (ASD) carrying missense mutations in MDGA1: p.Val116Met/p.Ala688Val and p.Tyr635Cys/p.Glu756Gln. Murine in utero overexpression of MDGA1 p.Val116Met/p.Ala688Val alters normal cortical neuron migration and impairs ultrasonic vocalizations (USVs). The p.Tyr635Cys/p.Glu756Gln substitution disrupts the triangular extracellular structure of MDGA1 and renders it unable to impact GABAergic synapses in hippocampal CA1 neurons. Male Mdga1 knock-in (KI) mouse pups and adults harboring the p.Tyr636Cys/p.Glu751Gln mutation exhibit impaired USVs

SUBMITTER: Seungjoon Kim 

PROVIDER: S-SCDT-10_1038-S44321-026-00402-Y | biostudies-other |

REPOSITORIES: biostudies-other