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It is mainly caused by pathogenetic variants in the X-linked MECP2 gene, encoding an epigenetic factor crucial for brain functioning. Despite intensive studies, the RTT pathogenetic mechanism remains to be fully elucidated. Impaired vascular function has been previously reported in RTT mouse models; however, whether an altered brain vascular homeostasis and the subsequent blood\u2013brain barrier (BBB) breakdown occur in RTT and contribute to the disease-related cognitive impairment is still unknown. Interestingly, in symptomatic Mecp2-null (Mecp2-\/y, Mecp2tm1.1Bird) mice, we found enhanced BBB permeability associated with an aberrant expression of the tight junction proteins Ocln and Cldn-5 in different brain areas, in terms of both transcript and protein levels. Additionally, Mecp2-null mice showed an altered expression of different genes encoding factors with a role in the BBB structure and function, such as Cldn3, Cldn12, Mpdz, Jam2, and Aqp4. With this study, we provide the first evidence of impaired BBB integrity in RTT and highlight a potential new molecular hallmark of the disease that might open new perspectives for the setting-up of novel therapeutic strategies.<\/jats:p>","DOI":"10.3390\/biom13040606","type":"journal-article","created":{"date-parts":[[2023,3,28]],"date-time":"2023-03-28T06:15:15Z","timestamp":1679984115000},"page":"606","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Blood\u2013Brain Barrier Integrity Is Perturbed in a Mecp2-Null Mouse Model of Rett Syndrome"],"prefix":"10.3390","volume":"13","author":[{"given":"Giuseppe","family":"Pepe","sequence":"first","affiliation":[{"name":"IRCCS Neuromed, 86077 Pozzilli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1345-4434","authenticated-orcid":false,"given":"Salvatore","family":"Fioriniello","sequence":"additional","affiliation":[{"name":"Institute of Genetics and Biophysics \u2018A. Buzzati-Traverso\u2019, CNR, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Federico","family":"Marracino","sequence":"additional","affiliation":[{"name":"IRCCS Neuromed, 86077 Pozzilli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luca","family":"Capocci","sequence":"additional","affiliation":[{"name":"IRCCS Neuromed, 86077 Pozzilli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vittorio","family":"Maglione","sequence":"additional","affiliation":[{"name":"IRCCS Neuromed, 86077 Pozzilli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4783-7572","authenticated-orcid":false,"given":"Maurizio","family":"D\u2019Esposito","sequence":"additional","affiliation":[{"name":"IRCCS Neuromed, 86077 Pozzilli, Italy"},{"name":"Institute of Genetics and Biophysics \u2018A. Buzzati-Traverso\u2019, CNR, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alba","family":"Di Pardo","sequence":"additional","affiliation":[{"name":"IRCCS Neuromed, 86077 Pozzilli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1643-6418","authenticated-orcid":false,"given":"Floriana","family":"Della Ragione","sequence":"additional","affiliation":[{"name":"IRCCS Neuromed, 86077 Pozzilli, Italy"},{"name":"Institute of Genetics and Biophysics \u2018A. 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