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Hypertension, Vol 18, 689-693, Copyright © 1991 by American Heart Association
L Simonet, E St. Lezin and TW Kurtz
In the inbred Dahl salt-sensitive rat (SS/Jr strain), it has been proposed
that a T for A transversion in the DNA sequence encoding amino acid 276 in
the alpha 1 subunit isoform of Na+,K(+)-ATPase may impair ion transport and
contribute to the pathogenesis of hypertension. This hypothesis is of major
scientific interest because it represents the first attempt to explain the
pathogenesis of salt-sensitive hypertension on the basis of a specifically
defined mutation at the DNA level. We devised a polymerase chain reaction
technique to screen the genomic DNA of multiple SS/Jr rats for the T for A
transversion reported in the complementary DNA (cDNA) encoding the alpha 1
subunit of Na+,K(+)-ATPase. When eight Dahl SS/Jr rats from Harlan Sprague
Dawley Inc. were tested with the polymerase chain reaction technique, we
found no evidence of this mutation in the Na+,K(+)-ATPase gene. Direct
sequence analysis of the gene in three SS/Jr rats also did not show the T
for A transversion. These results 1) strongly suggest that commercially
available Dahl SS/Jr rats do not carry a T for A transversion in the
genomic DNA sequence encoding amino acid 276 in the alpha 1 subunit isoform
of Na+,K(+)-ATPase and 2) raise the possibility that the previous finding
of a mutation in the cDNA of the SS/Jr rat may have been due to a reverse
transcriptase error during cDNA synthesis.
ARTICLES
Sequence analysis of the alpha 1 Na+,K(+)-ATPase gene in the Dahl salt- sensitive rat
Department of Laboratory Medicine, University of California, San Francisco 94143-0134.
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