Polymorphisms in the carboxy-terminus of the epithelial sodium channel in rat models for hypertension

Stefan Gründer, Laura Zagato, Chana Yagil, Yoram Yagil, Jean Sassard, Bernard C. Rossier

Research output: Contribution to journalArticle

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Abstract

Objective. To investigate whether mutations in the C-terminus of the three subunits of the rat epithelial sodium channel (αβγ-rENaC) contribute to the hypertensive phenotype in five rat models for essential hypertension. Design. We sequenced the C-terminal regions of α-, β- and γ-rENaC genes in five different hypertensive rat strains [spontaneously hypertensive rats (SHR), Dahl salt-sensitive (SS/Jr) rats, Milan hypertensive (MHS) rats, Sabra hypertensive (SBH) rats and Lyon hypertensive rats (LHR)] and their normotensive controls [Wistar-Kyoto (WKY) rats, Dahl salt-resistant (SR/Jr) rats, Milan normotensive (MNS) rats, Sabra normotensive (SBN) rats and Lyon normotensive rats (LNR)]. Identified polymorphisms were tested for cosegregation with blood pressure as well as for increased epithelial sodium channel (ENaC) activity. Methods. Genomic DNA extracted from hypertensive and normotensive rat strains was amplified by the polymerase chain reaction and polymerase chain reaction fragments were sequenced. Cosegregation analysis was performed to test for correlations between blood pressure and different genotypes. The effects of a polymorphism on ENaC activity were assessed by functional expression in Xenopos laevis oocytes. The chromosomal location of the gene for γ-ENaC was determined by linkage analysis in an F2 (MHS x MNS) population. Results. We found no polymorphisms at the C-terminus of α- and β-rENaC in the five rat models tested. We identified two polymorphisms at the C-terminus of the γ-subunit, one leading to an amino acid change. Milan strains (MNS and MHS) were polymorphic for this mutation, By cosegregation analysis we could exclude the possibility that there was a correlation between blood pressure and this polymorphism. Functional expression of the polymorphism caused no increase in ENaC activity assessed by measurement of the amiloride-sensitive sodium current in Xenopus oocytes. The gene for the γ-ENAC was located on rat chromosome Conclusions No polymorphisms at the C-terminus of the three subunits of the epithelial sodium channel cosegregating with blood pressure were detected in five different genetic rat models for hypertension. If an altered ENaC activity contributes to the pathogenesis of hypertension in these rats, it must thus arise from mutations in other parts of the protein, from mutations outside the coding region impairing the proper regulation of one of the subunits or from mutations in an ENaC-associated protein.

Original languageEnglish
Pages (from-to)173-179
Number of pages7
JournalJournal of Hypertension
Volume15
Issue number2
DOIs
Publication statusPublished - 1997

Fingerprint

Epithelial Sodium Channels
Hypertension
Mutation
Blood Pressure
Oocytes
Salts
Genes
Polymerase Chain Reaction
Inbred WKY Rats
Amiloride
Genetic Models
Inbred SHR Rats
Xenopus

Keywords

  • Epithelial sodium channel
  • Hypertension
  • Inbred rats
  • Linkage analysis
  • Rat chromosome 1

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology

Cite this

Polymorphisms in the carboxy-terminus of the epithelial sodium channel in rat models for hypertension. / Gründer, Stefan; Zagato, Laura; Yagil, Chana; Yagil, Yoram; Sassard, Jean; Rossier, Bernard C.

In: Journal of Hypertension, Vol. 15, No. 2, 1997, p. 173-179.

Research output: Contribution to journalArticle

Gründer, Stefan ; Zagato, Laura ; Yagil, Chana ; Yagil, Yoram ; Sassard, Jean ; Rossier, Bernard C. / Polymorphisms in the carboxy-terminus of the epithelial sodium channel in rat models for hypertension. In: Journal of Hypertension. 1997 ; Vol. 15, No. 2. pp. 173-179.
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abstract = "Objective. To investigate whether mutations in the C-terminus of the three subunits of the rat epithelial sodium channel (αβγ-rENaC) contribute to the hypertensive phenotype in five rat models for essential hypertension. Design. We sequenced the C-terminal regions of α-, β- and γ-rENaC genes in five different hypertensive rat strains [spontaneously hypertensive rats (SHR), Dahl salt-sensitive (SS/Jr) rats, Milan hypertensive (MHS) rats, Sabra hypertensive (SBH) rats and Lyon hypertensive rats (LHR)] and their normotensive controls [Wistar-Kyoto (WKY) rats, Dahl salt-resistant (SR/Jr) rats, Milan normotensive (MNS) rats, Sabra normotensive (SBN) rats and Lyon normotensive rats (LNR)]. Identified polymorphisms were tested for cosegregation with blood pressure as well as for increased epithelial sodium channel (ENaC) activity. Methods. Genomic DNA extracted from hypertensive and normotensive rat strains was amplified by the polymerase chain reaction and polymerase chain reaction fragments were sequenced. Cosegregation analysis was performed to test for correlations between blood pressure and different genotypes. The effects of a polymorphism on ENaC activity were assessed by functional expression in Xenopos laevis oocytes. The chromosomal location of the gene for γ-ENaC was determined by linkage analysis in an F2 (MHS x MNS) population. Results. We found no polymorphisms at the C-terminus of α- and β-rENaC in the five rat models tested. We identified two polymorphisms at the C-terminus of the γ-subunit, one leading to an amino acid change. Milan strains (MNS and MHS) were polymorphic for this mutation, By cosegregation analysis we could exclude the possibility that there was a correlation between blood pressure and this polymorphism. Functional expression of the polymorphism caused no increase in ENaC activity assessed by measurement of the amiloride-sensitive sodium current in Xenopus oocytes. The gene for the γ-ENAC was located on rat chromosome Conclusions No polymorphisms at the C-terminus of the three subunits of the epithelial sodium channel cosegregating with blood pressure were detected in five different genetic rat models for hypertension. If an altered ENaC activity contributes to the pathogenesis of hypertension in these rats, it must thus arise from mutations in other parts of the protein, from mutations outside the coding region impairing the proper regulation of one of the subunits or from mutations in an ENaC-associated protein.",
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AU - Zagato, Laura

AU - Yagil, Chana

AU - Yagil, Yoram

AU - Sassard, Jean

AU - Rossier, Bernard C.

PY - 1997

Y1 - 1997

N2 - Objective. To investigate whether mutations in the C-terminus of the three subunits of the rat epithelial sodium channel (αβγ-rENaC) contribute to the hypertensive phenotype in five rat models for essential hypertension. Design. We sequenced the C-terminal regions of α-, β- and γ-rENaC genes in five different hypertensive rat strains [spontaneously hypertensive rats (SHR), Dahl salt-sensitive (SS/Jr) rats, Milan hypertensive (MHS) rats, Sabra hypertensive (SBH) rats and Lyon hypertensive rats (LHR)] and their normotensive controls [Wistar-Kyoto (WKY) rats, Dahl salt-resistant (SR/Jr) rats, Milan normotensive (MNS) rats, Sabra normotensive (SBN) rats and Lyon normotensive rats (LNR)]. Identified polymorphisms were tested for cosegregation with blood pressure as well as for increased epithelial sodium channel (ENaC) activity. Methods. Genomic DNA extracted from hypertensive and normotensive rat strains was amplified by the polymerase chain reaction and polymerase chain reaction fragments were sequenced. Cosegregation analysis was performed to test for correlations between blood pressure and different genotypes. The effects of a polymorphism on ENaC activity were assessed by functional expression in Xenopos laevis oocytes. The chromosomal location of the gene for γ-ENaC was determined by linkage analysis in an F2 (MHS x MNS) population. Results. We found no polymorphisms at the C-terminus of α- and β-rENaC in the five rat models tested. We identified two polymorphisms at the C-terminus of the γ-subunit, one leading to an amino acid change. Milan strains (MNS and MHS) were polymorphic for this mutation, By cosegregation analysis we could exclude the possibility that there was a correlation between blood pressure and this polymorphism. Functional expression of the polymorphism caused no increase in ENaC activity assessed by measurement of the amiloride-sensitive sodium current in Xenopus oocytes. The gene for the γ-ENAC was located on rat chromosome Conclusions No polymorphisms at the C-terminus of the three subunits of the epithelial sodium channel cosegregating with blood pressure were detected in five different genetic rat models for hypertension. If an altered ENaC activity contributes to the pathogenesis of hypertension in these rats, it must thus arise from mutations in other parts of the protein, from mutations outside the coding region impairing the proper regulation of one of the subunits or from mutations in an ENaC-associated protein.

AB - Objective. To investigate whether mutations in the C-terminus of the three subunits of the rat epithelial sodium channel (αβγ-rENaC) contribute to the hypertensive phenotype in five rat models for essential hypertension. Design. We sequenced the C-terminal regions of α-, β- and γ-rENaC genes in five different hypertensive rat strains [spontaneously hypertensive rats (SHR), Dahl salt-sensitive (SS/Jr) rats, Milan hypertensive (MHS) rats, Sabra hypertensive (SBH) rats and Lyon hypertensive rats (LHR)] and their normotensive controls [Wistar-Kyoto (WKY) rats, Dahl salt-resistant (SR/Jr) rats, Milan normotensive (MNS) rats, Sabra normotensive (SBN) rats and Lyon normotensive rats (LNR)]. Identified polymorphisms were tested for cosegregation with blood pressure as well as for increased epithelial sodium channel (ENaC) activity. Methods. Genomic DNA extracted from hypertensive and normotensive rat strains was amplified by the polymerase chain reaction and polymerase chain reaction fragments were sequenced. Cosegregation analysis was performed to test for correlations between blood pressure and different genotypes. The effects of a polymorphism on ENaC activity were assessed by functional expression in Xenopos laevis oocytes. The chromosomal location of the gene for γ-ENaC was determined by linkage analysis in an F2 (MHS x MNS) population. Results. We found no polymorphisms at the C-terminus of α- and β-rENaC in the five rat models tested. We identified two polymorphisms at the C-terminus of the γ-subunit, one leading to an amino acid change. Milan strains (MNS and MHS) were polymorphic for this mutation, By cosegregation analysis we could exclude the possibility that there was a correlation between blood pressure and this polymorphism. Functional expression of the polymorphism caused no increase in ENaC activity assessed by measurement of the amiloride-sensitive sodium current in Xenopus oocytes. The gene for the γ-ENAC was located on rat chromosome Conclusions No polymorphisms at the C-terminus of the three subunits of the epithelial sodium channel cosegregating with blood pressure were detected in five different genetic rat models for hypertension. If an altered ENaC activity contributes to the pathogenesis of hypertension in these rats, it must thus arise from mutations in other parts of the protein, from mutations outside the coding region impairing the proper regulation of one of the subunits or from mutations in an ENaC-associated protein.

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