Utilization of a mutagenesis screen to generate mouse models of hyperaldosteronism

Ariadni Spyroglou, Sibylle Wagner, Celso Gomez-Sanchez, Birgit Rathkolb, Eckhard Wolf, Jenny Manolopoulou, Martin Reincke, Martin Bidlingmaier, Martin Hrabé De Angelis, Felix Beuschlein

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Primary aldosteronism is considered to be responsible for almost 10% of all cases of arterial hypertension. The genetic background of this common disease, however, has been elucidated only for the rare familial types, whereas in the large majority of sporadic cases, underlying mechanisms still remain unclear. In an attempt to define novel genetic loci involved in the pathophysiology of primary aldosteronism, a mutagenesis screen after treatment of mice with the alkylating agent N-ethyl-N-nitrosourea was established for the parameter aldosterone. As the detectionmethodwe used a time-resolved fluorescence immunoassay that allows the measurement of aldosterone in very small murine sample volumes. Based on this assay,wefirst determined the normal aldosterone values for wild-type C3HeB/FeJ mice under baseline conditions [92 ± 6 pg/ml for females (n = 69) and 173 ± 16 pg/ml for males (n = 55)]. Subsequently, aldosterone measurement was carried out in more than 2800 F 1 offspring of chemically mutagenized C3HeB/FeJ mice, and values were compared with aldosterone levels from untreated animals. Persistent hyperaldosteronism (defined as levels +3 SD above the mean of untreated animals) upon repeated measurements was present in seven female and two male F 1 offspring. Further breeding of these founders gave rise to F 2 pedigrees from which eight lines with different patterns of inheritance of hyperaldosteronism could be established. These animals will serve for detailed phenotypic and genetic characterization in the future. Taken together, our data demonstrate the feasibility of a phenotypedriven mutagenesis screen to detect and establish mutant mouse lines with a phenotype of chronic hyperaldosteronism.

Original languageEnglish
Pages (from-to)326-331
Number of pages6
JournalEndocrinology
Volume152
Issue number1
DOIs
StatePublished - Jan 2011
Externally publishedYes

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