{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T14:19:07Z","timestamp":1784557147336,"version":"3.55.0"},"reference-count":37,"publisher":"Bioscientifica","issue":"2","content-domain":{"domain":["jme.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2017,2]]},"abstract":"\n In an attempt to define novel genetic loci involved in the pathophysiology of primary aldosteronism, a mutagenesis screen after treatment with the alkylating agent\n N<\/jats:italic>\n -ethyl-\n N<\/jats:italic>\n -nitrosourea was established for the parameter aldosterone. One of the generated mouse lines with hyperaldosteronism was phenotypically and genetically characterized. This mouse line had high aldosterone levels but normal creatinine and urea values. The steroidogenic enzyme expression levels in the adrenal gland did not differ significantly among phenotypically affected and unaffected mice. Upon exome sequencing, point mutations were identified in seven candidate genes (\n Sspo<\/jats:italic>\n ,\n Dguok<\/jats:italic>\n ,\n Hoxaas2<\/jats:italic>\n ,\n Clstn3<\/jats:italic>\n ,\n Atm<\/jats:italic>\n ,\n Tipin<\/jats:italic>\n and\n Mapk6<\/jats:italic>\n ). Subsequently, animals were stratified into wild-type and mutated groups according to their genotype for each of these candidate genes. A correlation of their genotypes with the respective aldosterone, aldosterone-to-renin ratio (ARR), urea and creatinine values as well as steroidogenic enzyme expression levels was performed. Aldosterone values were significantly higher in animals carrying mutations in four different genes (\n Sspo<\/jats:italic>\n ,\n Dguok<\/jats:italic>\n ,\n Hoxaas2<\/jats:italic>\n and\n Clstn3<\/jats:italic>\n ) and associated statistically significant adrenal\n Cyp11b2<\/jats:italic>\n overexpression as well as increased ARR was present only in mice with\n Sspo<\/jats:italic>\n mutation. In contrast, mutations of the remaining candidate genes (\n Atm<\/jats:italic>\n ,\n Tipin<\/jats:italic>\n and\n Mapk6<\/jats:italic>\n ) were associated with lower aldosterone values and lower\n Hsd3b6<\/jats:italic>\n expression levels. In summary, these data demonstrate association between the genes\n Sspo<\/jats:italic>\n ,\n Dguok<\/jats:italic>\n ,\n Hoxaas2<\/jats:italic>\n and\n Clstn3<\/jats:italic>\n and hyperaldosteronism. Final proofs for the causative nature of the mutations have to come from knock-out and knock-in experiments.\n <\/jats:p>","DOI":"10.1530\/jme-16-0200","type":"journal-article","created":{"date-parts":[[2016,12,13]],"date-time":"2016-12-13T20:45:20Z","timestamp":1481661920000},"page":"67-78","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-6","source":"Crossref","is-referenced-by-count":6,"title":["Genetic characterization of a mouse line with primary aldosteronism"],"prefix":"10.1530","volume":"58","author":[{"given":"L G","family":"Perez-Rivas","sequence":"first","affiliation":[{"name":"1Medizinische Klinik und Poliklinik IVEndocrine Research Unit, Klinikum der Universit\u00e4t M\u00fcnchen, LMU, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y","family":"Rhayem","sequence":"additional","affiliation":[{"name":"1Medizinische Klinik und Poliklinik IVEndocrine Research Unit, Klinikum der Universit\u00e4t M\u00fcnchen, LMU, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Sabrautzki","sequence":"additional","affiliation":[{"name":"2Helmholtz Zentrum M\u00fcnchenGerman Research Center for Environmental Health (GmbH), Institute of Experimental Genetics and German Mouse Clinic, Neuherberg, Germany"},{"name":"3Helmholtz Zentrum M\u00fcnchenGerman Research Center for Environmental Health (GmbH), Research Unit Comparative Medicine, Neuherberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Hantel","sequence":"additional","affiliation":[{"name":"1Medizinische Klinik und Poliklinik IVEndocrine Research Unit, Klinikum der Universit\u00e4t M\u00fcnchen, LMU, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B","family":"Rathkolb","sequence":"additional","affiliation":[{"name":"2Helmholtz Zentrum M\u00fcnchenGerman Research Center for Environmental Health (GmbH), Institute of Experimental Genetics and German Mouse Clinic, Neuherberg, Germany"},{"name":"4Member of German Center for Diabetes Research (DZD)Neuherberg, Germany"},{"name":"5Ludwig-Maximilians-Universit\u00e4t M\u00fcnchenChair for Molecular Animal Breeding and Biotechnology, Gene Center of the M\u00fcnchen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Hrab\u011b de Angelis","sequence":"additional","affiliation":[{"name":"2Helmholtz Zentrum M\u00fcnchenGerman Research Center for Environmental Health (GmbH), Institute of Experimental Genetics and German Mouse Clinic, Neuherberg, Germany"},{"name":"4Member of German Center for Diabetes Research (DZD)Neuherberg, Germany"},{"name":"6Lehrstuhl f\u00fcr Experimentelle GenetikTechnische Universit\u00e4t M\u00fcnchen, Freising-Weihenstephan, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Reincke","sequence":"additional","affiliation":[{"name":"1Medizinische Klinik und Poliklinik IVEndocrine Research Unit, 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