{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T09:35:03Z","timestamp":1779183303937,"version":"3.51.4"},"reference-count":78,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,6,15]],"date-time":"2022-06-15T00:00:00Z","timestamp":1655251200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Health","award":["1R01HL140468"],"award-info":[{"award-number":["1R01HL140468"]}]},{"name":"Miami Heart Research Institute","award":["1R01HL140468"],"award-info":[{"award-number":["1R01HL140468"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Alport syndrome (AS) is a hereditary renal disorder with no etiological therapy. In the preclinical Col4a3-\/- model of AS, disease progression and severity vary depending on mouse strain. The sodium-glucose cotransporter 2 (SGLT2) is emerging as an attractive therapeutic target in cardiac\/renal pathologies, but its application to AS remains untested. This study investigates cardiorespiratory function and SGLT2 renal expression in Col4a3-\/- mice from three different genetic backgrounds, 129x1\/SvJ, C57Bl\/6 and Balb\/C. male Col4a3-\/- 129x1\/SvJ mice displayed alterations consistent with heart failure with preserved ejection fraction (HFpEF). Female, but not male, C57Bl\/6 and Balb\/C Col4a3-\/- mice exhibited mild changes in systolic and diastolic function of the heart by echocardiography. Male C57Bl\/6 Col4a3-\/- mice presented systolic dysfunction by invasive hemodynamic analysis. All strains except Balb\/C males demonstrated alterations in respiratory function. SGLT2 expression was significantly increased in AS compared to WT mice from all strains. However, cardiorespiratory abnormalities and SGLT2 over-expression were significantly less in AS Balb\/C mice compared to the other two strains. Systolic blood pressure was significantly elevated only in mutant 129x1\/SvJ mice. The results provide further evidence for strain-dependent cardiorespiratory and hypertensive phenotype variations in mouse AS models, corroborated by renal SGLT2 expression, and support ongoing initiatives to develop SGLT2 inhibitors for the treatment of AS.<\/jats:p>","DOI":"10.3390\/ijms23126674","type":"journal-article","created":{"date-parts":[[2022,6,15]],"date-time":"2022-06-15T22:17:01Z","timestamp":1655331421000},"page":"6674","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Col4a3-\/- Mice on Balb\/C Background Have Less Severe Cardiorespiratory Phenotype and SGLT2 Over-Expression Compared to 129x1\/SvJ and C57Bl\/6 Backgrounds"],"prefix":"10.3390","volume":"23","author":[{"given":"Camila I.","family":"Irion","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Cardiology, Leonard M. Miller School of Medicine, University of Miami, Miami, FL 33136, USA"},{"name":"Leonard M. Miller School of Medicine, Interdisciplinary Stem Cell Institute, University of Miami, Miami, FL 33136, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monique","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Cardiology, Leonard M. Miller School of Medicine, University of Miami, Miami, FL 33136, USA"},{"name":"Leonard M. Miller School of Medicine, Interdisciplinary Stem Cell Institute, University of Miami, Miami, FL 33136, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jose Condor","family":"Capcha","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Cardiology, Leonard M. Miller School of Medicine, University of Miami, Miami, FL 33136, USA"},{"name":"Leonard M. Miller School of Medicine, Interdisciplinary Stem Cell Institute, University of Miami, Miami, FL 33136, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Trevor","family":"Eisenberg","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Cardiology, Leonard M. Miller School of Medicine, University of Miami, Miami, FL 33136, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guerline","family":"Lambert","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Cardiology, Leonard M. Miller School of Medicine, University of Miami, Miami, FL 33136, USA"},{"name":"Leonard M. Miller School of Medicine, Interdisciplinary Stem Cell Institute, University of Miami, Miami, FL 33136, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lauro M.","family":"Takeuchi","sequence":"additional","affiliation":[{"name":"Leonard M. Miller School of Medicine, Interdisciplinary Stem Cell Institute, University of Miami, Miami, FL 33136, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Grace","family":"Seo","sequence":"additional","affiliation":[{"name":"Department of Medical Education, Leonard M. Miller School of Medicine, University of Miami, Miami, FL 33136, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keyvan","family":"Yousefi","sequence":"additional","affiliation":[{"name":"Leonard M. Miller School of Medicine, Interdisciplinary Stem Cell Institute, University of Miami, Miami, FL 33136, USA"},{"name":"Department of Molecular and Cellular Pharmacology, Leonard M. Miller School of Medicine, University of Miami, Miami, FL 33136, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosemeire","family":"Kanashiro-Takeuchi","sequence":"additional","affiliation":[{"name":"Leonard M. Miller School of Medicine, Interdisciplinary Stem Cell Institute, University of Miami, Miami, FL 33136, USA"},{"name":"Department of Molecular and Cellular Pharmacology, Leonard M. Miller School of Medicine, University of Miami, Miami, FL 33136, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keith A.","family":"Webster","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Cullen Eye Institute, Baylor College of Medicine, Houston, TX 77030, USA"},{"name":"Department of Ophthalmology, Vascular Biology Institute, Leonard M. Miller School of Medicine, University of Miami, Miami, FL 33136, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karen C.","family":"Young","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Leonard M. Miller School of Medicine, University of Miami, Miami, FL 33136, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7751-5032","authenticated-orcid":false,"given":"Joshua M.","family":"Hare","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Cardiology, Leonard M. Miller School of Medicine, University of Miami, Miami, FL 33136, USA"},{"name":"Leonard M. Miller School of Medicine, Interdisciplinary Stem Cell Institute, University of Miami, Miami, FL 33136, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2095-9326","authenticated-orcid":false,"given":"Lina A.","family":"Shehadeh","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Cardiology, Leonard M. Miller School of Medicine, University of Miami, Miami, FL 33136, USA"},{"name":"Leonard M. Miller School of Medicine, Interdisciplinary Stem Cell Institute, University of Miami, Miami, FL 33136, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.matbio.2016.08.005","article-title":"Collagen IV diseases: A focus on the glomerular basement membrane in Alport syndrome","volume":"57\u201358","author":"Cosgrove","year":"2017","journal-title":"Matrix Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1007\/s10157-018-1629-4","article-title":"A review of clinical characteristics and genetic backgrounds in Alport syndrome","volume":"23","author":"Nozu","year":"2019","journal-title":"Clin. Exp. 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