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1559-11826072023JulMolecular neurobiologyMol NeurobiolDystrophin Short Product, Dp71, Interacts with AQP4 and Kir4.1 Channels in the Mouse Cerebellar Glial Cells in Contrast to Dp427 at Inhibitory Postsynapses in the Purkinje Neurons.366436773664-367710.1007/s12035-023-03296-wDystrophin is the causative gene for Duchenne and Becker muscular dystrophy (DMD/BMD), and it produces full-length and short dystrophin, Dp427 and Dp71, respectively, in the brain. The existence of the different dystrophin molecular complexes has been known for a quarter century, so it is necessary to derive precise expression profiles of the molecular complexes in the brain to elucidate the mechanism of cognitive symptoms in DMD/BMD patients. In order to investigate the Dp71 expression profile in cerebellum, we employed Dp71-specific tag-insertion mice, which allowed for the specific detection of endogenous Dp71 in the immunohistochemical analysis and found its expressions in the glial cells, Bergmann glial (BG) cells, and astrocytes, whereas Dp427 was exclusively expressed in the inhibitory postsynapses within cerebellar Purkinje cells (PCs). Interestingly, we found different cell-type dependent dystrophin molecular complexes; i.e., glia-associated Dp71 was co-expressed with dystroglycan (DG) and dystrobrevinα, whereas synapse-associated Dp427 was co-expressed with DG and dystrobrevinβ. Furthermore, we investigated the molecular relationship of Dp71 to the AQP4 water channel and the Kir4.1 potassium channel, and found biochemical associations of Dp71 with AQP4 and Kir4.1 in both the cerebellum and cerebrum. Immunohistochemical and cytochemical investigations revealed partial co-localizations of Dp71 with AQP4 and Kir4.1 in the glial cells, indicating Dp71 interactions with the channels in the BG cells and astrocytes. Taken together, different cell-types, glial cells and Purkinje neurons, in the cerebellum express different dystrophin molecular complexes, which may contribute to pathological and physiological processes through the regulation of the water/ion channel and inhibitory postsynapses.© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.FujimotoTakahiroT0000-0002-9975-7008Department of Pathology and Applied Neurobiology, Kyoto Prefectural University of Medicine Graduate School of Medical Science, 465 Kajii-Cho, Kawaramachi Hirokoji, Kamigyo-Ku, Kyoto, 602-8566, Japan. tfuji@koto.kpu-m.ac.jp.StamKirstenKDepartment of Pathology and Applied Neurobiology, Kyoto Prefectural University of Medicine Graduate School of Medical Science, 465 Kajii-Cho, Kawaramachi Hirokoji, Kamigyo-Ku, Kyoto, 602-8566, Japan.YaoiTakeshiTDepartment of Pathology and Applied Neurobiology, Kyoto Prefectural University of Medicine Graduate School of Medical Science, 465 Kajii-Cho, Kawaramachi Hirokoji, Kamigyo-Ku, Kyoto, 602-8566, Japan.NakanoKentaKDepartment of Laboratory Animal Medicine, National Center for Global Health and Medicine (NCGM), Research Institute, Tokyo, 162-8655, Japan.AraiTetsuyaTDepartment of Laboratory Animal Medicine, National Center for Global Health and Medicine (NCGM), Research Institute, Tokyo, 162-8655, Japan.OkamuraTadashiTDepartment of Laboratory Animal Medicine, National Center for Global Health and Medicine (NCGM), Research Institute, Tokyo, 162-8655, Japan.ItohKyokoKDepartment of Pathology and Applied Neurobiology, Kyoto Prefectural University of Medicine Graduate School of Medical Science, 465 Kajii-Cho, Kawaramachi Hirokoji, Kamigyo-Ku, Kyoto, 602-8566, Japan. kxi14@koto.kpu-m.ac.jp.eng18K07883MEXT KAKENHI21K07279MEXT KAKENHI20A1019Grants-in-Aid for Research from the National Center for Global Health and Medicine21A1018Grants-in-Aid for Research from the National Center for Global Health and MedicineJournal Article20230315
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