Funktionelle und pathophysiologische Untersuchung neuer Mutationen des Natrium-Chlorid-Cotransporters der Niere beim Gitelman Syndrom

Das Gitelman Syndrom ist eine autosomal rezessiv vererbte renale Tubulopathie, die durch eine hypokalämische Alkalose, eine Hypomagnesiämie und eine Hypocalciurie charakterisiert ist. Die Erkrankung basiert auf Mutationen im SCL12A3 Gen, das für den Natrium-Chlorid-Transporter (NCCT) im distalen Abs...

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Bibliographic Details
Main Author: Knop, Caroline
Contributors: Waldegger, Siegfried (Prof. Dr.) (Thesis advisor)
Format: Doctoral Thesis
Language:German
Published: Philipps-Universität Marburg 2010
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Table of Contents: Gitelmans syndrome is an autosomal recessiv renal tubular dissorder characterized by hypokalemic, metabolic alkalosis, hypomagnesemia and hypocalciuria. This disorder results from mutations in the NaCl cotransporter. To elucidate the functional implications of the mutations, Cl-uptakes were determined in Xenopus laevis oocytes expressing wild-typ or mutant NCCT. All mutants exhibited no significant Cl uptake. In Western blot all mutant proteins were represented. Only one mutation (T180R) was not represented in the Western blot analysis. Immunocytochemical analysis showed the lokalisation of the mutant proteins. One mutant protein (R83W) was found only below the plasma membrane, three (G731R, R887Q und V1015M) could be detected at and below the oocyte plasma membrane and three (R135C, D486N und S614P) could only detected at the membrane like the wild typ. In conclusion, this study substantiates NCCT processing defects as the underlying pathogenic mechanism in Gitelmansyndrome. A correlation between the functional analysis and the varity of the symptomes in Gitelman patient could not shown with this study.