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Clinical assessments and limited brain imaging studies of patients with PMS have uncovered regional volume reductions and white matter thinning. While these impairments have been replicated ex vivo in pups of a rat model, brain structure has not been assessed in rats in vivo or in adults. We assessed the brain structure of heterozygous and homozygous adult\n                    <jats:italic>Shank3<\/jats:italic>\n                    \u2010deficient male rats in comparison to wild\u2010type littermates with magnetic resonance imaging using both anatomical assessments and diffusion tensor imaging (DTI).\n                    <jats:italic>Shank3<\/jats:italic>\n                    \u2010deficient rats showed a reduction in overall brain size and the absolute volume of the neocortex, piriform cortex, thalamus, forebrain, inferior and superior colliculi, internal capsule, and anterior commissure. The superior colliculus was decreased in relative volume. DTI revealed that axial diffusion and fractional anisotropy were reduced in the external capsule and mean diffusion was increased in the fornix, suggesting that restriction of diffusion perpendicular to the axis of the axonal fibers was impaired in these white matter tracts. Therefore,\n                    <jats:italic>Shank3<\/jats:italic>\n                    \u2010deficient rats replicate the reduced brain volume and altered white matter phenotypes present in PMS. Our results indicate that the loss of a glutamatergic synaptic protein, Shank3, has structural consequences at the level of the whole brain. The brain regions that were altered represent potential cross\u2010species structural biomarkers that warrant further study.\n                  <\/jats:p>","DOI":"10.1002\/aur.2568","type":"journal-article","created":{"date-parts":[[2021,7,27]],"date-time":"2021-07-27T06:38:56Z","timestamp":1627367936000},"page":"1837-1842","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Reduced brain volume and white matter alterations in\n                    <i>Shank3<\/i>\n                    \u2010deficient rats"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1445-3724","authenticated-orcid":false,"given":"Carla E. M.","family":"Golden","sequence":"first","affiliation":[{"name":"Department of Psychiatry Icahn School of Medicine at Mount Sinai  New York New York USA"},{"name":"Seaver Autism Center for Research and Treatment Icahn School of Medicine at Mount Sinai  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria X.","family":"Wang","sequence":"additional","affiliation":[{"name":"BioMedical Engineering and Imaging Institute Icahn School of Medicine at Mount Sinai  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hala","family":"Harony\u2010Nicolas","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Icahn School of Medicine at Mount Sinai  New York New York USA"},{"name":"Seaver Autism Center for Research and Treatment Icahn School of Medicine at Mount Sinai  New York New York USA"},{"name":"Nash Family Department of Neuroscience Icahn School of Medicine at Mount Sinai  New York New York USA"},{"name":"Friedman Brain Institute Icahn School of Medicine at Mount Sinai  New York New York USA"},{"name":"Mindich Child Health and Development Institute Icahn School of Medicine at Mount Sinai  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick R.","family":"Hof","sequence":"additional","affiliation":[{"name":"Seaver Autism Center for Research and Treatment Icahn School of Medicine at Mount Sinai  New York New York USA"},{"name":"Nash Family Department of Neuroscience Icahn School of Medicine at Mount Sinai  New York New York USA"},{"name":"Friedman Brain Institute Icahn School of Medicine at Mount Sinai  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph D.","family":"Buxbaum","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Icahn School of Medicine at Mount Sinai  New York New York USA"},{"name":"Seaver Autism Center for Research and Treatment Icahn School of Medicine at Mount Sinai  New York New York USA"},{"name":"Nash Family Department of Neuroscience Icahn School of Medicine at Mount Sinai  New York New York USA"},{"name":"Friedman Brain Institute Icahn School of Medicine at Mount Sinai  New York New York USA"},{"name":"Mindich Child Health and Development Institute Icahn School of Medicine at Mount Sinai  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,7,27]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.35700"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2020.01.006"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/aur.1925"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fninf.2013.00015"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13229-018-0205-9"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1159\/000503840"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/aur.1883"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-020-00943-x"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1177\/0883073815600872"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.18904"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.50959"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09965"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2007-2584"},{"key":"e_1_2_6_15_1","volume-title":"R: 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