Loss of Katnal2 leads to ependymal ciliary hyperfunction and autism-related phenotypes in mice.

Autor: Kang R; Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea.; Center for Synaptic Brain Dysfunctions, Institute for Basic Science (IBS), Daejeon, Korea., Kim K; Center for Synaptic Brain Dysfunctions, Institute for Basic Science (IBS), Daejeon, Korea., Jung Y; Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea., Choi SH; Center for Neuroscience Imaging Research, Institute for Basic Science (IBS), Suwon, Korea.; Department of Biomedical Engineering, Sungkyunkwan University, Suwon, Korea., Lee C; Center for Neuroscience Imaging Research, Institute for Basic Science (IBS), Suwon, Korea., Im GH; Center for Neuroscience Imaging Research, Institute for Basic Science (IBS), Suwon, Korea., Shin M; Department of Biological Sciences, Sookmyung Women's University, Seoul, Korea., Ryu K; Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea., Choi S; Department of Biological Sciences, Sookmyung Women's University, Seoul, Korea., Yang E; Department of Anatomy, Biomedical Sciences, College of Medicine, Korea University, Seoul, Korea., Shin W; Center for Synaptic Brain Dysfunctions, Institute for Basic Science (IBS), Daejeon, Korea., Lee S; Center for Synaptic Brain Dysfunctions, Institute for Basic Science (IBS), Daejeon, Korea., Lee S; Center for Synaptic Brain Dysfunctions, Institute for Basic Science (IBS), Daejeon, Korea., Papadopoulos Z; Neuroscience Graduate Program, School of Medicine, Washington University in St. Louis, St. Louis, Missouri, United States of America., Ahn JH; Center for Vascular Research, Institute for Basic Science (IBS), Daejeon, Korea., Koh GY; Center for Vascular Research, Institute for Basic Science (IBS), Daejeon, Korea., Kipnis J; Neuroscience Graduate Program, School of Medicine, Washington University in St. Louis, St. Louis, Missouri, United States of America.; Brain Immunology and Glia (BIG) Center, Washington University in St. Louis, St. Louis, Missouri, United States of America.; Department of Pathology and Immunology, School of Medicine, Washington University in St. Louis, St. Louis, Missouri, United States of America., Kang H; Division of National Supercomputing, Korea Institute of Science and Technology Information (KISTI), Daejeon, Korea., Kim H; Department of Anatomy, Biomedical Sciences, College of Medicine, Korea University, Seoul, Korea., Cho WK; Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea., Park S; Department of Biological Sciences, Sookmyung Women's University, Seoul, Korea., Kim SG; Center for Neuroscience Imaging Research, Institute for Basic Science (IBS), Suwon, Korea.; Department of Biomedical Engineering, Sungkyunkwan University, Suwon, Korea., Kim E; Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea.; Center for Synaptic Brain Dysfunctions, Institute for Basic Science (IBS), Daejeon, Korea.
Jazyk: angličtina
Zdroj: PLoS biology [PLoS Biol] 2024 May 08; Vol. 22 (5), pp. e3002596. Date of Electronic Publication: 2024 May 08 (Print Publication: 2024).
DOI: 10.1371/journal.pbio.3002596
Abstrakt: Autism spectrum disorders (ASD) frequently accompany macrocephaly, which often involves hydrocephalic enlargement of brain ventricles. Katnal2 is a microtubule-regulatory protein strongly linked to ASD, but it remains unclear whether Katnal2 knockout (KO) in mice leads to microtubule- and ASD-related molecular, synaptic, brain, and behavioral phenotypes. We found that Katnal2-KO mice display ASD-like social communication deficits and age-dependent progressive ventricular enlargements. The latter involves increased length and beating frequency of motile cilia on ependymal cells lining ventricles. Katnal2-KO hippocampal neurons surrounded by enlarged lateral ventricles show progressive synaptic deficits that correlate with ASD-like transcriptomic changes involving synaptic gene down-regulation. Importantly, early postnatal Katnal2 re-expression prevents ciliary, ventricular, and behavioral phenotypes in Katnal2-KO adults, suggesting a causal relationship and a potential treatment. Therefore, Katnal2 negatively regulates ependymal ciliary function and its deletion in mice leads to ependymal ciliary hyperfunction and hydrocephalus accompanying ASD-related behavioral, synaptic, and transcriptomic changes.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2024 Kang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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