Conditional gene targeting of the ENaC subunit genes Scnn1b and Scnn1g.
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-, beta-, and gamma-ENaC). Since complete gene inactivation of the beta- 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 beta- 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.
Mérillat
Anne-Marie
AM
Département de Pharmacologie et de Toxicologie, Univ. of Lausanne, Rue du Bugnon 27, CH-1005 Lausanne, Switzerland.
Charles
Roch-Philippe
RP
Porret
Andrée
A
Maillard
Marc
M
Rossier
Bernard
B
Beermann
Friedrich
F
Hummler
Edith
E
D000450:Aldosterone / Q000097:blood*; D000483:Alleles; D000818:Animals; D053503:Epithelial Sodium Channels / Q000235:genetics*; D015870:Gene Expression; D018390:Gene Targeting; D051379:Mice; D008822:Mice, Transgenic; D011188:Potassium / Q000097:blood; D012333:RNA, Messenger / Q000235:genetics; D012964:Sodium / Q000097:blood
D053503:Epithelial Sodium Channels; D012333:RNA, Messenger; C507049:Scnn1b protein, mouse; C507053:Scnn1g protein, mouse; D000450:Aldosterone; D012964:Sodium; D011188:Potassium