{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T01:24:30Z","timestamp":1790645070646,"version":"4.1.0"},"reference-count":62,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2023,6,21]],"date-time":"2023-06-21T00:00:00Z","timestamp":1687305600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002426","name":"Telethon","doi-asserted-by":"publisher","award":["GGP14065"],"award-info":[{"award-number":["GGP14065"]}],"id":[{"id":"10.13039\/501100002426","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Sickle cell disease (SCD) is caused by the homozygous beta-globin gene mutation that can lead to ischemic multi-organ damage and consequently reduce life expectancy. On the other hand, sickle cell trait (SCT), the heterozygous beta-globin gene mutation, is still considered a benign condition. Although the mechanisms are not well understood, clinical evidence has recently shown that specific pathological symptoms can also be recognized in SCT carriers. So far, there are still scant data regarding the morphological modifications referable to possible multi-organ damage in the SCT condition. Therefore, after genotypic and hematological characterization, by conventional light microscopy and transmission electron microscopy (TEM), we investigated the presence of tissue alterations in 13 heterozygous Townes mice, one of the best-known animal models that, up to now, was used only for the study of the homozygous condition. We found that endothelial alterations, as among which the thickening of vessel basal lamina, are ubiquitous in the lung, liver, kidney, and spleen of SCT carrier mice. The lung shows the most significant alterations, with a distortion of the general tissue architecture, while the heart is the least affected. Collectively, our findings contribute novel data to the histopathological modifications at microscopic and ultrastructural levels, underlying the heterozygous beta-globin gene mutation, and indicate the translational suitability of the Townes model to characterize the features of multiple organ involvement in the SCT carriers.<\/jats:p>","DOI":"10.3390\/ijms241310452","type":"journal-article","created":{"date-parts":[[2023,6,22]],"date-time":"2023-06-22T01:49:32Z","timestamp":1687398572000},"page":"10452","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Multi-Organ Morphological Findings in a Humanized Murine Model of Sickle Cell Trait"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4725-0413","authenticated-orcid":false,"given":"Marcello","family":"Trucas","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, Section of Cytomorphology, University of Cagliari, Cittadella Universitaria di Monserrato, 09042 Monserrato, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Burattini","sequence":"additional","affiliation":[{"name":"Department of Biomolecular Sciences, Campus Scientifico \u201cEnrico Mattei\u201d, University of Urbino Carlo Bo, Via Ca\u2019 le Suore 2\u2014Localit\u00e0 Crocicchia, 61029 Urbino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8053-7075","authenticated-orcid":false,"given":"Susanna","family":"Porcu","sequence":"additional","affiliation":[{"name":"Italian National Research Council (CNR)\u2014IRGB, Cittadella Universitaria Monserrato, 09042 Monserrato, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michela","family":"Simbula","sequence":"additional","affiliation":[{"name":"Italian National Research Council (CNR)\u2014IRGB, Cittadella Universitaria Monserrato, 09042 Monserrato, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4122-9293","authenticated-orcid":false,"given":"Maria Serafina","family":"Ristaldi","sequence":"additional","affiliation":[{"name":"Italian National Research Council (CNR)\u2014IRGB, Cittadella Universitaria Monserrato, 09042 Monserrato, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta Anna","family":"Kowalik","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Unit of Oncology and Molecular Pathology, University of Cagliari, Cittadella Universitaria di Monserrato, 09042 Monserrato, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3343-7861","authenticated-orcid":false,"given":"Maria Pina","family":"Serra","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Section of Cytomorphology, University of Cagliari, Cittadella Universitaria di Monserrato, 09042 Monserrato, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4705-0833","authenticated-orcid":false,"given":"Pietro","family":"Gobbi","sequence":"additional","affiliation":[{"name":"Department of Biomolecular Sciences, Campus Scientifico \u201cEnrico Mattei\u201d, University of Urbino Carlo Bo, Via Ca\u2019 le Suore 2\u2014Localit\u00e0 Crocicchia, 61029 Urbino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michela","family":"Battistelli","sequence":"additional","affiliation":[{"name":"Department of Biomolecular Sciences, Campus Scientifico \u201cEnrico Mattei\u201d, University of Urbino Carlo Bo, Via Ca\u2019 le Suore 2\u2014Localit\u00e0 Crocicchia, 61029 Urbino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8098-899X","authenticated-orcid":false,"given":"Andrea","family":"Perra","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Unit of Oncology and Molecular Pathology, University of Cagliari, Cittadella Universitaria di Monserrato, 09042 Monserrato, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1884-3597","authenticated-orcid":false,"given":"Marina","family":"Quartu","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Section of Cytomorphology, University of Cagliari, Cittadella Universitaria di Monserrato, 09042 Monserrato, 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