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Data from neuroimaging studies suggest white matter microstructure aberrations across these conditions. In 16p11.2 deletion and duplication carriers, potential gene dosage effects may impact white matter organisation, contributing to phenotypes including impaired cognition. However, the biological mechanisms underlying this white matter pathology remain unclear. To bridge this knowledge gap, we utilised mouse models of 16p11.2 deletion and duplication to explore changes in corpus callosum oligodendrocytes, myelination, axon caliber, and astrocytes. Immunofluorescence staining was employed to measure lineage and mature oligodendrocyte numbers, as well as myelin basic protein and glial fibrillary acidic protein fluorescence intensity. Transmission electron microscopy was utilised to evaluate axonal structural alterations related to myelin, such as myelinated axon percentage, diameter, myelin thickness, and g-ratio. Our findings reveal changes in the number of mature oligodendrocytes, myelination levels, axon diameter, and astrocytes in the corpus callosum of mice with 16p11.2 deletion and duplication. Deletion mice displayed a tendency toward reduced counts of mature oligodendrocytes and myelination levels, while duplication mice exhibited a notable increase. Axon diameter variations included a significant increase in axon diameter and myelin thickness in both deletion and duplication mice, but with irregular structure in duplication mice. Variances in astrocytes between genotypes showed significant early increases in development for both deletion and duplication mice compared to wild-type mice, with this rise sustained in duplication mice but significantly diminished in deletion mice at a later stage. Our research reveals changes in the biological mechanisms impacting white matter. Comparison of reciprocal trends in 16p11.2 deletion and duplication mice with wild-type mice suggests the possibility of gene dosage effects. Identification of these mechanisms offers an initial step in unveiling therapeutic targets for associated neurodevelopmental disorder phenotypes.<\/jats:p>","DOI":"10.3390\/ijms26020573","type":"journal-article","created":{"date-parts":[[2025,1,13]],"date-time":"2025-01-13T07:40:08Z","timestamp":1736754008000},"page":"573","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Mice with 16p11.2 Deletion and Duplication Show Alterations in Biological Processes Associated with White Matter"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-3741-0386","authenticated-orcid":false,"given":"Tianqi","family":"Wang","sequence":"first","affiliation":[{"name":"Neuroscience and Mental Health Innovation Institute, Cardiff University, Hadyn Ellis Building, Cardiff CF24 4HQ, UK"},{"name":"School of Bioscience, Cardiff University, The Sir Martin Evans Building, Museum Ave., Cardiff CF10 3AX, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Megan","family":"Sharp","sequence":"additional","affiliation":[{"name":"Neuroscience and Mental Health Innovation Institute, Cardiff University, Hadyn Ellis Building, Cardiff CF24 4HQ, UK"},{"name":"School of Bioscience, Cardiff University, The Sir Martin Evans Building, Museum Ave., Cardiff CF10 3AX, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5691-5400","authenticated-orcid":false,"given":"Ilaria","family":"Morella","sequence":"additional","affiliation":[{"name":"Neuroscience and Mental Health Innovation Institute, Cardiff University, Hadyn Ellis Building, Cardiff CF24 4HQ, UK"},{"name":"School of Bioscience, Cardiff University, The Sir Martin Evans Building, Museum Ave., Cardiff CF10 3AX, UK"},{"name":"Department of Biology and Biotechnology \u201cLazzaro Spallanzani\u201d, University of Pavia, Via Adolfo Ferrata, 9, 27100 Pavia, PV, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6651-0041","authenticated-orcid":false,"given":"Francesco","family":"Bedogni","sequence":"additional","affiliation":[{"name":"Neuroscience and Mental Health Innovation Institute, Cardiff University, Hadyn Ellis Building, Cardiff CF24 4HQ, UK"},{"name":"School of Medicine, Cardiff University, McKenzie House, 30\u201336 Newport Road, Cardiff CF24 0DE, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8369-9501","authenticated-orcid":false,"given":"Vladimir","family":"Trajkovski","sequence":"additional","affiliation":[{"name":"Institute of Special Education and Rehabilitation, Faculty of Philosophy, University \u201cSs. Cyril and Methodius\u201d, Blvd. Goce Delchev 9A, 1000 Skopje, North Macedonia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Riccardo","family":"Brambilla","sequence":"additional","affiliation":[{"name":"Neuroscience and Mental Health Innovation Institute, Cardiff University, Hadyn Ellis Building, Cardiff CF24 4HQ, UK"},{"name":"School of Bioscience, Cardiff University, The Sir Martin Evans Building, Museum Ave., Cardiff CF10 3AX, UK"},{"name":"Department of Biology and Biotechnology \u201cLazzaro Spallanzani\u201d, University of Pavia, Via Adolfo Ferrata, 9, 27100 Pavia, PV, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9495-307X","authenticated-orcid":false,"given":"Yasir Ahmed","family":"Syed","sequence":"additional","affiliation":[{"name":"Neuroscience and Mental Health Innovation Institute, Cardiff University, Hadyn Ellis Building, Cardiff CF24 4HQ, UK"},{"name":"School of Bioscience, Cardiff University, The Sir Martin Evans Building, Museum Ave., Cardiff CF10 3AX, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"American Psychiatric Association (2022). 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