{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T22:48:36Z","timestamp":1776293316835,"version":"3.50.1"},"reference-count":94,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T00:00:00Z","timestamp":1755561600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Natural Sciences and Engineering Research Council of Canada Discovery Grant (NSERC-DG)","award":["RGPIN-2024-04920"],"award-info":[{"award-number":["RGPIN-2024-04920"]}]},{"name":"Natural Sciences and Engineering Research Council of Canada Discovery Grant (NSERC-DG)","award":["202209PJT-486512-CIA-CDAA-111824"],"award-info":[{"award-number":["202209PJT-486512-CIA-CDAA-111824"]}]},{"name":"Ontario Rett Syndrome Association (ORSA) Hope Fund","award":["RGPIN-2024-04920"],"award-info":[{"award-number":["RGPIN-2024-04920"]}]},{"name":"Ontario Rett Syndrome Association (ORSA) Hope Fund","award":["202209PJT-486512-CIA-CDAA-111824"],"award-info":[{"award-number":["202209PJT-486512-CIA-CDAA-111824"]}]},{"name":"Children\u2019s Hospital Research Institute of Manitoba (CHRIM) Operating Grant","award":["RGPIN-2024-04920"],"award-info":[{"award-number":["RGPIN-2024-04920"]}]},{"name":"Children\u2019s Hospital Research Institute of Manitoba (CHRIM) Operating Grant","award":["202209PJT-486512-CIA-CDAA-111824"],"award-info":[{"award-number":["202209PJT-486512-CIA-CDAA-111824"]}]},{"name":"University of Manitoba Collaborative Research Grant (UCRP)","award":["RGPIN-2024-04920"],"award-info":[{"award-number":["RGPIN-2024-04920"]}]},{"name":"University of Manitoba Collaborative Research Grant (UCRP)","award":["202209PJT-486512-CIA-CDAA-111824"],"award-info":[{"award-number":["202209PJT-486512-CIA-CDAA-111824"]}]},{"name":"Canadian Institutes of Health Research (CIHR) Project Grant","award":["RGPIN-2024-04920"],"award-info":[{"award-number":["RGPIN-2024-04920"]}]},{"name":"Canadian Institutes of Health Research (CIHR) Project Grant","award":["202209PJT-486512-CIA-CDAA-111824"],"award-info":[{"award-number":["202209PJT-486512-CIA-CDAA-111824"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Methyl CpG-binding protein 2 (MeCP2) is an epigenetic reader of DNA methylation with high abundance in the brain. While genetic mutations occur across different protein domains of MeCP2, the T158M mutation is amongst the most frequent MeCP2 mutations. MeCP2 is encoded by the MECP2\/Mecp2 gene located on the X chromosome. In humans, MECP2 mutations cause Rett Syndrome, a debilitating neurodevelopmental disorder in females, with very rare cases presenting in males. Despite the generation of different transgenic mouse lines with MeCP2 mutations, the sex-dependent phenotypic and molecular impact of common MeCP2 mutations in mouse models of disease remains largely unexplored. Here, we focus on the MeCP2 T158M mutation using Mecp2tm4.1Bird\/J transgenic mice (referred to as Mecp2T158M), and report that Mecp2T158M mutant mice display sex-specific molecular, behavioural, and phenotypic characteristics when compared to wild-type controls. Our data indicates sex- and brain-region-dependent impacts on the expression of MeCP2, synaptic proteins, cytoskeletal markers, and autophagy factors. Our findings demonstrate that the phenotypic and molecular characteristics of this mouse model may relate to the clinical manifestation in human patients with Rett Syndrome.<\/jats:p>","DOI":"10.3390\/cells14161286","type":"journal-article","created":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T15:29:29Z","timestamp":1755617369000},"page":"1286","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Mutation of MeCP2 at T158M Leads to Distinct Molecular and Phenotypic Abnormalities in Male and Female Mice"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-8872-5542","authenticated-orcid":false,"given":"Chris-Tiann","family":"Roberts","sequence":"first","affiliation":[{"name":"Biochemistry and Medical Genetics, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, 745 Bannatyne Avenue, Basic Medical Sciences Bldg. Room 627, Winnipeg, MB R3E 0J9, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-8641-7969","authenticated-orcid":false,"given":"Ashraf","family":"Kadar Shahib","sequence":"additional","affiliation":[{"name":"Biochemistry and Medical Genetics, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, 745 Bannatyne Avenue, Basic Medical Sciences Bldg. Room 627, Winnipeg, MB R3E 0J9, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Khatereh Saei","family":"Arezoumand","sequence":"additional","affiliation":[{"name":"Biochemistry and Medical Genetics, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, 745 Bannatyne Avenue, Basic Medical Sciences Bldg. Room 627, Winnipeg, MB R3E 0J9, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ghanan Bin","family":"Akhtar","sequence":"additional","affiliation":[{"name":"Biochemistry and Medical Genetics, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, 745 Bannatyne Avenue, Basic Medical Sciences Bldg. Room 627, Winnipeg, MB R3E 0J9, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazem","family":"Nejati-Koshki","sequence":"additional","affiliation":[{"name":"Biochemistry and Medical Genetics, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, 745 Bannatyne Avenue, Basic Medical Sciences Bldg. Room 627, Winnipeg, MB R3E 0J9, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica S.","family":"Jarmasz","sequence":"additional","affiliation":[{"name":"Biochemistry and Medical Genetics, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, 745 Bannatyne Avenue, Basic Medical Sciences Bldg. Room 627, Winnipeg, MB R3E 0J9, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seyyed Mohyeddin","family":"Ziaee","sequence":"additional","affiliation":[{"name":"Biochemistry and Medical Genetics, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, 745 Bannatyne Avenue, Basic Medical Sciences Bldg. Room 627, Winnipeg, MB R3E 0J9, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marjorie","family":"Buist","sequence":"additional","affiliation":[{"name":"Biochemistry and Medical Genetics, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, 745 Bannatyne Avenue, Basic Medical Sciences Bldg. Room 627, Winnipeg, MB R3E 0J9, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicole","family":"Raabe","sequence":"additional","affiliation":[{"name":"Biochemistry and Medical Genetics, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, 745 Bannatyne Avenue, Basic Medical Sciences Bldg. Room 627, Winnipeg, MB R3E 0J9, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abbas","family":"Rezaeian Mehrabadi","sequence":"additional","affiliation":[{"name":"Biochemistry and Medical Genetics, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, 745 Bannatyne Avenue, Basic Medical Sciences Bldg. Room 627, Winnipeg, MB R3E 0J9, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carl O.","family":"Olson","sequence":"additional","affiliation":[{"name":"Biochemistry and Medical Genetics, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, 745 Bannatyne Avenue, Basic Medical Sciences Bldg. Room 627, Winnipeg, MB R3E 0J9, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3619-6116","authenticated-orcid":false,"given":"Mojgan","family":"Rastegar","sequence":"additional","affiliation":[{"name":"Biochemistry and Medical Genetics, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, 745 Bannatyne Avenue, Basic Medical Sciences Bldg. Room 627, Winnipeg, MB R3E 0J9, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/S1044-7431(03)00026-5","article-title":"Expression of MeCP2 in olfactory receptor neurons is developmentally regulated and occurs before synaptogenesis","volume":"22","author":"Cohen","year":"2003","journal-title":"Mol. 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