TY  - JOUR
U1  - Zeitschriftenartikel, wissenschaftlich - begutachtet (reviewed)
A1  - Gettings, Sean M.
A1  - Maxeiner, Stephan
A1  - Tzika, Maria
A1  - Cobain, Matthew R. D.
A1  - Ruf, Irina
A1  - Benseler, Fritz
A1  - Brose, Nils
A1  - Krasteva-Christ, Gabriela
A1  - Vande Velde, Greetje
A1  - Schönberger, Matthias
A1  - Althaus, Mike
T1  - Two Functional Epithelial Sodium Channel Isoforms Are Present in Rodents despite Pronounced Evolutionary Pseudogenization and Exon Fusion
JF  - Molecular Biology and Evolution
N2  - The epithelial sodium channel (ENaC) plays a key role in salt and water homeostasis in tetrapod vertebrates. There are four ENaC subunits (α, β, γ, δ), forming heterotrimeric αβγ- or δβγ-ENaCs. While the physiology of αβγ-ENaC is well understood, for decades the field has stalled with respect to δβγ-ENaC due to the lack of mammalian model organisms. The SCNN1D gene coding for δ-ENaC was previously believed to be absent in rodents, hindering studies using standard laboratory animals. We analysed all currently available rodent genomes and discovered that SCNN1D is present in rodents but was independently lost in five rodent lineages, including the Muridae (mice and rats). The independent loss of SCNN1D in rodent lineages may be constrained by phylogeny and taxon-specific adaptation to dry habitats, however habitat aridity does not provide a selection pressure for maintenance of SCNN1D across Rodentia. A fusion of two exons coding for a structurally flexible region in the extracellular domain of δ-ENaC appeared in the Hystricognathi (a group that includes guinea pigs). This conserved pattern evolved at least 41 Ma ago and represents a new autapomorphic feature for this clade. Exon fusion does not impair functionality of guinea pig (Cavia porcellus) δβγ-ENaC expressed in Xenopus oocytes. Electrophysiological characterisation at the whole-cell and single-channel level revealed conserved biophysical features and mechanisms controlling guinea pig αβγ- and δβγ-ENaC function as compared to human orthologues. Guinea pigs therefore represent commercially available mammalian model animals that will help shed light on the physiological function of δ-ENaC.
KW  - exon fusion
KW  - pseudogene
KW  - SCNN1D
KW  - delta-subunit
KW  - rodent
KW  - ENaC
KW  - evolution
KW  - epithelial sodium channel
UN  - https://nbn-resolving.org/urn:nbn:de:hbz:1044-opus-58483
SN  - 0737-4038
SS  - 0737-4038
U6  - https://doi.org/10.1093/molbev/msab271
DO  - https://doi.org/10.1093/molbev/msab271
PM  - 34491346
VL  - 38
IS  - 12
SP  - 5704
EP  - 5725
PB  - Oxford University Press (OUP)
ER  -