264182 20231120155358.0 10.3389/fcell.2023.1243299 doi pmid:37745298 pmid pmc:PMC10511643 pmc altmetric:153873943 altmetric DZNE-2023-00962 English 570 Yildiz, Berra 0 Shank3 related muscular hypotonia is accompanied by increased intracellular calcium concentrations and ion channel dysregulation in striated muscle tissue. Lausanne 2023 Frontiers Media article DRIVER Output Types/Journal article DataCite Journal Article journal journal PUB:(DE-HGF)16 1696418970_23995 PUB:(DE-HGF) ARTICLE BibTeX JOURNAL_ARTICLE ORCID Journal Article 0 EndNote Phelan-McDermid syndrome (PMS) is a syndromic form of Autism Spectrum Disorders (ASD) classified as a rare genetic neurodevelopmental disorder featuring global developmental delay, absent or delayed speech, ASD-like behaviour and neonatal skeletal muscle hypotonia. PMS is caused by a heterozygous deletion of the distal end of chromosome 22q13.3 or SHANK3 mutations. We analyzed striated muscles of newborn Shank3Δ11(-/-) animals and found a significant enlargement of the sarcoplasmic reticulum as previously seen in adult Shank3Δ11(-/-) mice, indicative of a Shank3-dependent and not compensatory mechanism for this structural alteration. We analyzed transcriptional differences by RNA-sequencing of muscle tissue of neonatal Shank3Δ11(-/-) mice and compared those to Shank3(+/+) controls. We found significant differences in gene expression of ion channels crucial for muscle contraction and for molecules involved in calcium ion regulation. In addition, calcium storage- [i.e., Calsequestrin (CSQ)], calcium secretion- and calcium-related signaling-proteins were found to be affected. By immunostainings and Western blot analyses we could confirm these findings both in Shank3Δ11(-/-) mice and PMS patient muscle tissue. Moreover, alterations could be induced in vitro by the selective downregulation of Shank3 in C2C12 myotubes. Our results emphasize that SHANK3 levels directly or indirectly regulate calcium homeostasis in a cell autonomous manner that might contribute to muscular hypotonia especially seen in the newborn. 352 - Disease Mechanisms (POF4-352) G:(DE-HGF)POF4-352 POF4-352 POF IV 0 Dataset connected to CrossRef, PubMed, , Journals: pub.dzne.de ASD Other RNA-sequencing Other Shank3 Other immunohistochemistry Other muscular hypotonia Other neurodevelopmental disorders Other western blot Other Schiedt, Lisa 1 Mulaw, Medhanie 2 Bockmann, Jürgen 3 Jesse, Sarah P:(DE-2719)9001441 4 dzne Lutz, Anne-Kathrin 5 Boeckers, Tobias M P:(DE-2719)2812855 6 Last author dzne 10.3389/fcell.2023.1243299 Vol. 11, p. 1243299 PERI:(DE-600)2737824-X 1243299 Frontiers in cell and developmental biology 11 2023 2296-634X OpenAccess http://pub.dzne.de/record/264182/files/DZNE-2023-00962.pdf OpenAccess http://pub.dzne.de/record/264182/files/DZNE-2023-00962_SUPP.zip OpenAccess pdfa http://pub.dzne.de/record/264182/files/DZNE-2023-00962.pdf?subformat=pdfa oai:pub.dzne.de:264182 openaire open_access VDB driver dnbdelivery External Institute I:(DE-HGF)0 Extern 4 P:(DE-2719)9001441 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 6 P:(DE-2719)2812855 DE-HGF Gesundheit Neurodegenerative Diseases G:(DE-HGF)POF4-350 G:(DE-HGF)POF4-352 G:(DE-HGF)POF4 G:(DE-HGF)POF4-300 G:(DE-HGF)POF Disease Mechanisms 0 2023 DBCoverage StatID:(DE-HGF)0160 StatID Essential Science Indicators 2022-11-12 DBCoverage StatID:(DE-HGF)1190 StatID Biological Abstracts 2022-11-12 Creative Commons Attribution CC BY 4.0 LIC:(DE-HGF)CCBY4 HGFVOC DBCoverage StatID:(DE-HGF)0501 StatID DOAJ Seal 2021-05-13T10:29:32Z DBCoverage StatID:(DE-HGF)0500 StatID DOAJ 2021-05-13T10:29:32Z WoS StatID:(DE-HGF)0113 StatID Science Citation Index Expanded 2022-11-12 Fees StatID:(DE-HGF)0700 StatID 2022-11-12 OpenAccess StatID:(DE-HGF)0510 StatID Article Processing Charges StatID:(DE-HGF)0561 StatID 2022-11-12 Peer Review StatID:(DE-HGF)0030 StatID DOAJ : Anonymous peer review 2021-05-13T10:29:32Z JCR StatID:(DE-HGF)0100 StatID FRONT CELL DEV BIOL : 2022 2023-10-26 DBCoverage StatID:(DE-HGF)0200 StatID SCOPUS 2023-10-26 DBCoverage StatID:(DE-HGF)0300 StatID Medline 2023-10-26 DBCoverage StatID:(DE-HGF)0320 StatID PubMed Central 2023-10-26 DBCoverage StatID:(DE-HGF)0199 StatID Clarivate Analytics Master Journal List 2023-10-26 DBCoverage StatID:(DE-HGF)1050 StatID BIOSIS Previews 2023-10-26 DBCoverage StatID:(DE-HGF)0150 StatID Web of Science Core Collection 2023-10-26 IF >= 5 StatID:(DE-HGF)9905 StatID FRONT CELL DEV BIOL : 2022 2023-10-26 I:(DE-2719)1910002 AG Böckers Translational Protein Biochemistry 0 journal VDB UNRESTRICTED I:(DE-2719)1910002 FullTexts