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Loss of MECP2 protein is thought to cause Rett syndrome phenotypes. The specific underlying mechanisms from typical developmental trajectory to regression features throughout life are unclear. Lack of established timelines to study the molecular, cellular, and behavioral features of regression in female mouse models is a major contributing factor. Due to random X\u2010chromosome inactivation, female patients with Rett syndrome and female mouse models for Rett syndrome (\n                    <jats:italic>Mecp2<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>Heterozygous<\/jats:italic>\n                    <\/jats:sup>\n                    , Het) express a functional copy of wild\u2010type MECP2 protein in approximately half of all cells. As MECP2 expression is regulated during early postnatal development and experience, we characterized the expression of wild\u2010type MECP2 in the primary somatosensory cortex of female Het mice. Here, we report increased MECP2 levels in non\u2010parvalbumin\u2010positive neurons of 6\u2010week\u2010old adolescent Het relative to age\u2010matched wild\u2010type controls, while also displaying typical levels of perineuronal net expression in the barrel field subregion of the primary somatosensory cortex, mild tactile sensory perception deficits, and efficient pup retrieval behavior. In contrast, 12\u2010week\u2010old adult Het express MECP2 at levels similar to age\u2010matched wild\u2010type mice, show increased perineuronal net expression in the cortex, and display significant tactile sensory perception deficits. Thus, we have identified a set of behavioral metrics and the cellular substrates to study regression during a specific time in the female Het mouse model, which coincides with changes in wild\u2010type MECP2 expression. We speculate that the precocious increase in MECP2 expression within specific cell types of adolescent Het may provide compensatory benefits at the behavioral level, while the inability to further increase MECP2 levels leads to regressive behavioral phenotypes over time.\n                  <\/jats:p>","DOI":"10.1002\/jnr.25190","type":"journal-article","created":{"date-parts":[[2023,4,7]],"date-time":"2023-04-07T05:24:40Z","timestamp":1680845080000},"page":"1236-1258","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Wild\u2010type\n                    <scp>MECP2<\/scp>\n                    expression coincides with age\u2010dependent sensory phenotypes in a female mouse model for Rett syndrome"],"prefix":"10.1002","volume":"101","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3467-5308","authenticated-orcid":false,"given":"Michael","family":"Mykins","sequence":"first","affiliation":[{"name":"Department of 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Tennessee  Knoxville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra Hart","family":"McBryar","sequence":"additional","affiliation":[{"name":"Department of Biochemistry &amp; Cellular and Molecular Biology University of Tennessee  Knoxville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Perez","sequence":"additional","affiliation":[{"name":"Department of Biochemistry &amp; Cellular and Molecular Biology University of Tennessee  Knoxville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trinity Rose","family":"Shultz","sequence":"additional","affiliation":[{"name":"Department of Biochemistry &amp; Cellular and Molecular Biology University of Tennessee  Knoxville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7927-0745","authenticated-orcid":false,"given":"Andrew","family":"Willems","sequence":"additional","affiliation":[{"name":"Department of Biochemistry &amp; Cellular and Molecular Biology University of Tennessee  Knoxville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2380-5341","authenticated-orcid":false,"given":"Billy You Bun","family":"Lau","sequence":"additional","affiliation":[{"name":"Department of Biochemistry &amp; Cellular and Molecular Biology University of Tennessee  Knoxville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8212-7050","authenticated-orcid":false,"given":"Tian","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Biochemistry &amp; Cellular and Molecular Biology University of Tennessee  Knoxville Tennessee 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