Study of KATNAL2 associated with microtubule regulation and Autism Spectrum Disorder

Abstract

Autism Spectrum Disorders (

ASD) are genetic disorders that diagnosed by social deficits and repetitive behavior/restricted interested. Genome-wide association studies suggested genes driving pathology from diverse categories, like encoding channels, synapse molecules, chromosome remodelers, as well as genes with unknown CNS function. During those genes intuitively involved in neuronal functions are thoroughly researched, many of genes on the list were undermined even they are thought to be linked with ASD pathogenesis confidently. Here, I report deletion of Katnal2, associated with microtubule-severing function, causes mild social deficits, enormous transcriptomic changes with severe hydrocephalus in mice. Katnal2 KO male mice showed aberrant USV calls and social behaviors when they encountered female mice, while gene deletion have limited impact on neuronal properties. Meanwhile, Katnal2 KO induced vast transcriptomic alterations tend to ASD-prone and anti-proliferation and severe hydrocephaly. Throughout these diverse changes, lacking Katnal2 genes in mice induced sub-threshold alterations that would devastate genetic predispositions of ASD.