{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:20:12Z","timestamp":1792804812794,"version":"4.5.0"},"reference-count":32,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2024,5,7]],"date-time":"2024-05-07T00:00:00Z","timestamp":1715040000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) project","award":["314061271-TRR 205"],"award-info":[{"award-number":["314061271-TRR 205"]}],"id":[{"id":"https:\/\/ror.org\/018mejw64","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) project","award":["325768017"],"award-info":[{"award-number":["325768017"]}],"id":[{"id":"https:\/\/ror.org\/018mejw64","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) project","award":["205\/2 TP S01"],"award-info":[{"award-number":["205\/2 TP S01"]}],"id":[{"id":"https:\/\/ror.org\/018mejw64","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Heisenberg Professorship","award":["314061271-TRR 205"],"award-info":[{"award-number":["314061271-TRR 205"]}]},{"name":"Heisenberg Professorship","award":["325768017"],"award-info":[{"award-number":["325768017"]}]},{"name":"Heisenberg Professorship","award":["205\/2 TP S01"],"award-info":[{"award-number":["205\/2 TP S01"]}]},{"name":"DFG within the CRC\/Transregio","award":["314061271-TRR 205"],"award-info":[{"award-number":["314061271-TRR 205"]}]},{"name":"DFG within the CRC\/Transregio","award":["325768017"],"award-info":[{"award-number":["325768017"]}]},{"name":"DFG within the CRC\/Transregio","award":["205\/2 TP S01"],"award-info":[{"award-number":["205\/2 TP S01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Congenital Adrenal Hyperplasia (CAH) is an autosomal recessive disorder impairing cortisol synthesis due to reduced enzymatic activity. This leads to persistent adrenocortical overstimulation and the accumulation of precursors before the blocked enzymatic step. The predominant form of CAH arises from mutations in CYP21A2, causing 21-hydroxylase deficiency (21-OHD). Despite emerging treatment options for CAH, it is not always possible to physiologically replace cortisol levels and counteract hyperandrogenism. Moreover, there is a notable absence of an effective in vivo model for pre-clinical testing. In this work, we developed an animal model for CAH with the clinically relevant point mutation p.R484Q in the previously humanized CYP21A2 mouse strain. Mutant mice showed hyperplastic adrenals and exhibited reduced levels of corticosterone and 11-deoxycorticosterone and an increase in progesterone. Female mutants presented with higher aldosterone concentrations, but blood pressure remained similar between wildtype and mutant mice in both sexes. Male mutant mice have normal fertility with a typical testicular appearance, whereas female mutants are infertile, exhibit an abnormal ovarian structure, and remain in a consistent diestrus phase. Conclusively, we show that the animal model has the potential to contribute to testing new treatment options and to prevent comorbidities that result from hormone-related derangements and treatment-related side effects in CAH patients.<\/jats:p>","DOI":"10.3390\/ijms25105062","type":"journal-article","created":{"date-parts":[[2024,5,7]],"date-time":"2024-05-07T06:53:27Z","timestamp":1715064807000},"page":"5062","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["A Humanized and Viable Animal Model for Congenital Adrenal Hyperplasia\u2013CYP21A2-R484Q Mutant Mouse"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7360-7941","authenticated-orcid":false,"given":"Shamini Ramkumar","family":"Thirumalasetty","sequence":"first","affiliation":[{"name":"Division of Paediatric Endocrinology and Diabetes, Department of Paediatrics, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universit\u00e4t Dresden, 01307 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4845-5376","authenticated-orcid":false,"given":"Tina","family":"Schubert","sequence":"additional","affiliation":[{"name":"Division of Paediatric Endocrinology and Diabetes, Department of Paediatrics, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universit\u00e4t Dresden, 01307 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald","family":"Naumann","sequence":"additional","affiliation":[{"name":"Transgenic Core Facility, Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilka","family":"Reichardt","sequence":"additional","affiliation":[{"name":"Genome Engineering Facility, Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Luise","family":"Rohm","sequence":"additional","affiliation":[{"name":"Division of Paediatric Endocrinology and Diabetes, Department of Paediatrics, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universit\u00e4t Dresden, 01307 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dana","family":"Landgraf","sequence":"additional","affiliation":[{"name":"Division of Paediatric Endocrinology and Diabetes, Department of Paediatrics, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universit\u00e4t Dresden, 01307 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2739-345X","authenticated-orcid":false,"given":"Florian","family":"Gembardt","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Medizinische Klinik III, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universit\u00e4t Dresden, 01307 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirko","family":"Peitzsch","sequence":"additional","affiliation":[{"name":"Institute of Clinical Chemistry and Laboratory Medicine, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universit\u00e4t Dresden, 01307 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michaela F.","family":"Hartmann","sequence":"additional","affiliation":[{"name":"Steroid Research & Mass Spectrometry Unit, Paediatric Endocrinology and Diabetology, Center of Child and Adolescent Medicine, Justus Liebig Universit\u00e4t, 35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2895-4087","authenticated-orcid":false,"given":"Mihail","family":"Sarov","sequence":"additional","affiliation":[{"name":"Genome Engineering Facility, Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan A.","family":"Wudy","sequence":"additional","affiliation":[{"name":"Steroid Research & Mass Spectrometry Unit, Paediatric Endocrinology and Diabetology, Center of Child and Adolescent Medicine, Justus Liebig Universit\u00e4t, 35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Reisch","sequence":"additional","affiliation":[{"name":"Medizinische Klinik und Poliklinik IV, LMU Klinikum M\u00fcnchen, 80336 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Huebner","sequence":"additional","affiliation":[{"name":"Division of Paediatric Endocrinology and Diabetes, Department of Paediatrics, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universit\u00e4t Dresden, 01307 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrin","family":"Koehler","sequence":"additional","affiliation":[{"name":"Division of Paediatric Endocrinology and Diabetes, Department of Paediatrics, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universit\u00e4t Dresden, 01307 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1038\/s41574-022-00655-w","article-title":"Management challenges and therapeutic advances in congenital adrenal hyperplasia","volume":"18","author":"Mallappa","year":"2022","journal-title":"Nat. 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