The α1 Na,K-ATPase gene is a susceptibility hypertension gene in the Dahl salt-sensitiveHSD rat

被引:64
作者
Herrera, VLM
Xie, HX
Lopez, LV
Schork, NJ
Ruiz-Opazo, N
机构
[1] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA
[2] Boston Univ, Sch Med, Evans Dept Med, Cardiol Sect, Boston, MA 02118 USA
[3] Case Western Reserve Univ, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA
[4] Case Western Reserve Univ, Dept Genet, Cleveland, OH 44106 USA
关键词
hypertension; genetics; Na; K-ATPase; transgenic model; cosegregation analysis;
D O I
10.1172/JCI3868
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Despite the prevalence of essential hypertension, its underlying genetic basis has not been elucidated due to the complexities of its determinants. To identify a hypertension susceptibility gene, we used an approach that integrates molecular, transgenic, and genetic analysis using Dahl salt-sensitive (S) and Dahl salt-resistant (R) rats ascertained for genotype and phenotype. To determine the role of the Dahl S Q276L alpha 1 Na,K-ATPase gene variant, we developed transgenic Dahl S rats bearing the Dahl R wild-type (wt) oil Na,K-ATPase cDNA directed by the cognate wt promoter region, Tg[wt alpha 1]. Transgenic Dahl S rats exhibited less salt-sensitive hypertension, less hypertensive renal disease, and longer life span when compared with non-transgenic Dahl S controls. Total chromosome 2 linkage analysis of F2(SXR) male rats detects cosegregation of the cll Na,K-ATPase locus with salt-sensitive hypertension. These data support the alpha 1 Na,K-ATPase gene as a susceptibility gene for salt-sensitive hypertension in the Dahl S rat model, and provide the basis for the study of the alpha 1 Na,K-ATPase locus in human hypertension.
引用
收藏
页码:1102 / 1111
页数:10
相关论文
共 31 条
[1]  
CANESSA M, 1993, J MEMBRANE BIOL, V134, P107
[2]   Quantitative trait loci in genetically hypertensive rats - Possible sex specificity [J].
Clark, JS ;
Jeffs, B ;
Davidson, AO ;
Lee, WK ;
Anderson, NH ;
Bihoreau, MT ;
Brosnan, MJ ;
Devlin, AM ;
Kelman, AW ;
Lindpaintner, K ;
Dominiczak, AF .
HYPERTENSION, 1996, 28 (05) :898-906
[3]   GENETIC INFLUENCE OF KIDNEYS ON BLOOD-PRESSURE - EVIDENCE FROM CHRONIC RENAL HOMOGRAFTS IN RATS WITH OPPOSITE PREDISPOSITIONS TO HYPERTENSION [J].
DAHL, LK ;
HEINE, M ;
THOMPSON, K .
CIRCULATION RESEARCH, 1974, 34 (01) :94-101
[4]   ROLE OF GENETIC FACTORS IN SUSCEPTIBILITY TO EXPERIMENTAL HYPERTENSION DUE TO CHRONIC EXCESS SALT INGESTION [J].
DAHL, LK ;
HEINE, M ;
TASSINARI, L .
NATURE, 1962, 194 (4827) :480-&
[5]  
Dallner G, 1974, Methods Enzymol, V31, P191
[6]   MAPPING OF A QUANTITATIVE TRAIT LOCUS FOR BLOOD-PRESSURE ON RAT CHROMOSOME-2 [J].
DENG, AY ;
DENE, H ;
RAPP, JP .
JOURNAL OF CLINICAL INVESTIGATION, 1994, 94 (01) :431-436
[7]   THE PRIMARY ROLE OF THE KIDNEY AND SALT INTAKE IN THE ETIOLOGY OF ESSENTIAL-HYPERTENSION .2. [J].
DEWARDENER, HE .
CLINICAL SCIENCE, 1990, 79 (04) :289-297
[8]   GENETIC-DETERMINANTS OF DIASTOLIC AND PULSE PRESSURE MAP TO DIFFERENT LOCI IN LYON HYPERTENSIVE RATS [J].
DUBAY, C ;
VINCENT, M ;
SAMANI, NJ ;
HILBERT, P ;
KAISER, MA ;
BERESSI, JP ;
KOTELEVTSEV, Y ;
BECKMANN, JS ;
SOUBRIER, F ;
SASSARD, J ;
LATHROP, GM .
NATURE GENETICS, 1993, 3 (04) :354-357
[9]   Human genetics - High anxiety [J].
Goldman, D .
SCIENCE, 1996, 274 (5292) :1483-1483
[10]   A FAILURE ANALYSIS CASE-STUDY OF A RADIO TRANSMISSION TOWER [J].
HERRERA, JM ;
SPENCER, PR ;
TARIN, PM ;
STAFFORD, SW .
MATERIALS CHARACTERIZATION, 1995, 34 (01) :51-55