Dataset Information

Total and synaptosomal proteomic analysis

ABSTRACT: Autism spectrum disorders (ASD) represent neurodevelopmental disorders characterized by social deficits, repetitive behaviors, and various comorbidities, including epilepsy. ANK2, which encodes a neuronal scaffolding protein, is frequently mutated in ASD, but its in vivo functions and disease-related mechanisms are largely unknown. Here, we report that mice with Ank2 knockout restricted to cortical and hippocampal excitatory neurons (Ank2-cKO mice) show ASD-related behavioral abnormalities and juvenile seizure-related death. Ank2-cKO cortical neurons show abnormally increased excitability and firing rate. These changes accompanied decreases in the total level and function of the Kv7.2/KCNQ2 and Kv7.3/KCNQ3 potassium channels and the density of these channels in the enlengthened axon initial segment. Importantly, the Kv7 agonist, retigabine, rescued neuronal excitability, juvenile seizure-related death, and hyperactivity in Ank2-cKO mice. These results suggest that Ank2 regulates neuronal excitability by regulating the length of and Kv7 density in the AIS and that Kv7 channelopathy is involved in Ank2-related brain dysfunctions.

INSTRUMENT(S): Orbitrap Exploris 480

ORGANISM(S): Mus Musculus (ncbitaxon:10090)

SUBMITTER: Jin Young Kim

PROVIDER: MSV000091510 | MassIVE | Sun Mar 19 21:33:00 GMT 2023

SECONDARY ACCESSION(S): PXD040968

REPOSITORIES: MassIVE

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Kv7/KCNQ potassium channels in cortical hyperexcitability and juvenile seizure-related death in Ank2-mutant mice.

Oh Hyoseon H Lee Suho S Oh Yusang Y Kim Seongbin S Kim Young Seo YS Yang Yeji Y Choi Woochul W Yoo Ye-Eun YE Cho Heejin H Lee Seungjoon S Yang Esther E Koh Wuhyun W Won Woojin W Kim Ryunhee R Lee C Justin CJ Kim Hyun H Kang Hyojin H Kim Jin Young JY Ku Taeyun T Paik Se-Bum SB Kim Eunjoon E

Nature communications 20230615 1

Autism spectrum disorders (ASD) represent neurodevelopmental disorders characterized by social deficits, repetitive behaviors, and various comorbidities, including epilepsy. ANK2, which encodes a neuronal scaffolding protein, is frequently mutated in ASD, but its in vivo functions and disease-related mechanisms are largely unknown. Here, we report that mice with Ank2 knockout restricted to cortical and hippocampal excitatory neurons (Ank2-cKO mice) show ASD-related behavioral abnormalities and j ...[more]

PMID: 37321992

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