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Am J Physiol Renal Physiol 296: F249-F256, 2009. First published November 26, 2008; doi:10.1152/ajprenal.00612.2007
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Aldosterone and Epithelial Na+ Channel

Conditional gene targeting of the ENaC subunit genes Scnn1b and Scnn1g

Anne-Marie Mérillat,1,2 Roch-Philippe Charles,1 Andrée Porret,2 Marc Maillard,3 Bernard Rossier,1 Friedrich Beermann,4 and Edith Hummler1,2

1Département de Pharmacologie et de Toxicologie, 2Transgenic Animal Facility, and 3Service de Nephrologie du Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne; and 4ISREC (Swiss Institute for Experimental Cancer Research), School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Epalinges, Switzerland

Submitted 24 December 2007 ; accepted in final form 22 November 2008

Epithelial sodium channels (ENaC) are members of the degenerin/ENaC superfamily of non-voltage-gated, highly amiloride-sensitive cation channels that are composed of three subunits ({alpha}-, β-, and {gamma}-ENaC). Since complete gene inactivation of the β- and {gamma}-ENaC subunit genes (Scnn1b and Scnn1g) leads to early postnatal death, we generated conditional alleles and obtained mice harboring floxed and null alleles for both gene loci. Using quantitative RT-PCR analysis, we showed that the introduction of the loxP sites did not interfere with the mRNA transcript expression level of the Scnn1b and Scnn1g gene locus, respectively. Upon a regular and salt-deficient diet, both β- and {gamma}-ENaC floxed mice showed no difference in their mRNA transcript expression levels, plasma electrolytes, and aldosterone concentrations as well as weight changes compared with control animals. These mice can now be utilized to dissect the role of ENaC function in classical and nonclassic target organs/tissues.

transgenic; conditional knockout; epithelial sodium channel; amiloride-sensitive sodium channel; mouse model; β-ENaC; {gamma}-ENaC


Address for reprint requests and other correspondence: E. Hummler, Département de Pharmacologie et de Toxicologie, Univ. of Lausanne, Rue du Bugnon 27, CH-1005 Lausanne, Switzerland (e-mail: Edith.Hummler{at}unil.ch)






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