title: Mapping and sequence analysis of the gene encoding the beta subunit of the epithelial sodium channel in experimental models of hypertension.
abstract: OBJECTIVE
  To investigate whether mutations in the beta subunit of the epithelial sodium channel (Scnn1b) contribute to the pathogenesis of hypertension in the spontaneously hypertensive rat (SHR) and the Dahl salt-sensitive rat.
  
  
  METHODS
  We determined the chromosome location of the rat Scnn1b gene, tested for cosegregation with blood pressure, and sequenced near full-length Scnn1b complementary DNAs (cDNAs) from SHR and Dahl salt-sensitive rats.
  
  
  METHODS
  Chromosome mapping was performed by somatic cell hybrid analysis and by linkage analysis in recombinant inbred strains derived from SHR and Brown-Norway rats. Cosegregation analysis was performed by testing for correlations between blood pressure and Scnn1b genotypes in these strains. DNA sequencing was performed on cDNAs prepared from reverse-transcribed messenger RNA derived from rat kidney.
  
  
  RESULTS
  The Scnn1b gene was closely linked to the Sa gene on rat chromosome 1. Blood pressure correlated significantly with Scnn1b gene in the recombinant inbred strains. Analysis of near full-length Scnn1b cDNAs from SHR and Dahl rats failed to reveal any coding sequence mutations that could affect the predicted amino acid sequence of the Scnn1b protein.
  
  
  CONCLUSIONS
  The Scnn1b gene maps near the Sa gene in a region of rat chromosome 1 involved in the inherited control of blood pressure. If disordered activity of the epithelial cell sodium channel contributes to the pathogenesis of hypertension in the SHR or Dahl models, it must stem from genetic lesions in sequences that regulate Scnn1b function or in sequences important to the structure or function of the other sodium channel subunits.
authors.affiliation: Department of Laboratory Medicine, University of California, San Francisco, USA.
authors.forename: H
authors.initials: H
authors.lastname: Huang
authors.forename: M
authors.initials: M
authors.lastname: Pravenec
authors.forename: J M
authors.initials: JM
authors.lastname: Wang
authors.forename: V
authors.initials: V
authors.lastname: Kren
authors.forename: E
authors.initials: E
authors.lastname: St Lezin
authors.forename: C
authors.initials: C
authors.lastname: Szpirer
authors.forename: J
authors.initials: J
authors.lastname: Szpirer
authors.forename: T W
authors.initials: TW
authors.lastname: Kurtz
mesh_terms: D000818:Animals; D001483:Base Sequence; D001794:Blood Pressure; D002874:Chromosome Mapping; D004351:Drug Resistance / Q000235:genetics; D004848:Epithelium / Q000378:metabolism; D005796:Genes; D008040:Genetic Linkage; D006973:Hypertension / Q000235:genetics* / Q000503:physiopathology; D015335:Molecular Probes / Q000235:genetics; D008969:Molecular Sequence Data; D051381:Rats; D011918:Rats, Inbred SHR / Q000235:genetics; D011919:Rats, Inbred Strains / Q000235:genetics; D011995:Recombination, Genetic; D015222:Sodium Channels / Q000235:genetics*; D012965:Sodium Chloride / Q000494:pharmacology
chemical_list: D015335:Molecular Probes; D015222:Sodium Channels; D012965:Sodium Chloride