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Spyroglou, A.* ; Wagner, S. ; Gomez-Sanchez, C.* ; Rathkolb, B. ; Wolf, E. ; Manolopoulou, J.* ; Reincke, M.* ; Bidlingmaier, M.* ; Hrabě de Angelis, M. ; Beuschlein, F.*

Utilization of a mutagenesis screen to generate mouse models of hyperaldosteronism.

Endocrinology 152, 326-331 (2011)
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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 detection method we used a time-resolved fluorescence immunoassay that allows the measurement of aldosterone in very small murine sample volumes. Based on this assay, we first 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 phenotype-driven mutagenesis screen to detect and establish mutant mouse lines with a phenotype of chronic hyperaldosteronism.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords ETHYL-N-NITROSOUREA; ENU MUTAGENESIS; CHEMICAL MUTAGENESIS; PHENOTYPE-DRIVEN; LOCUS MUTATIONS; ADRENAL-GLAND; ETHYLNITROSOUREA; HYPERTENSION; ALDOSTERONE; INDUCTION
ISSN (print) / ISBN 0013-7227
e-ISSN 1945-7170
Journal Endocrinology
Quellenangaben Volume: 152, Issue: 1, Pages: 326-331 Article Number: , Supplement: ,
Publisher Endocrine Society
Publishing Place Chevy Chase, Md.
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Experimental Genetics (IEG)