Genetic isolation of a region of chromosome 8 that exerts major effects on blood pressure and cardiac mass in the spontaneously hypertensive rat.

Křen, Vladimı́r; Pravenec, Michal; Lu, Shanshan; Křenová, D; Wang, J M; Wang, N; Merriouns, T; Wong, A; Lezin, Elizabeth St.; Lau, David T. W.; Szpirer, Claude; Szpirer, Josiane; Kurtz, Theodore W.

doi:10.1172/jci119198

Cited by 80 publications

(47 citation statements)

References 23 publications

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“…45 No significant effect of the differential segment was found in some other studies, however. 28,46 …”

Section: Discussionmentioning

confidence: 99%

“…Both strains have been maintained at the Centre de recherche, Centre hospitalier de l'Université de Montréal (Montréal, Canada) since 1996, when they were transferred from the Czech Academy of Sciences in Prague (Czech Republic). 28 The congenic strain SHR.1N was derived from SHR/Ola (termed SHR from here onwards) and normotensive Brown Norway (BN.Lx/Cub) rats. It differs from SHR by a segment RNO20 that is of BN.Lx/Cub (called BN from here onwards) origin and includes the TNF-␣ gene 29 (Figure 1).…”

Section: Strainsmentioning

confidence: 99%

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Segment of Rat Chromosome 20 Regulates Diet-Induced Augmentations in Adiposity, Glucose Intolerance, and Blood Pressure

et al. 2003

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Abstract-Previous linkage and association studies have suggested that a region of human chromosome 6 containing the tumor necrosis factor (TNF)-␣ gene is involved in the pathogenesis of obesity and obesity-associated hypertension. The aim of the present investigation was to establish whether a segment of rat chromosome 20 (RNO20), which also contains the TNF-␣ gene, determines diet-induced changes in adiposity and blood pressure (BP). The results showed that a transfer of the RNO20 segment from the normotensive Brown Norway (BN) rat onto the background of the spontaneously hypertensive rat (SHR) is associated with a significantly greater increase in adiposity, glucose intolerance, circulating leptin levels, and BP during 12-week, high-fat-diet feeding. In contrast, the transfer is not associated with significant changes in these variables during 12-week, normal-diet feeding. In addition, sequencing of the TNF-␣ gene revealed differences between SHR and BN in the 5Ј-and 3Ј-regulatory regions of the gene. Subsequent analyses of TNF-␣ gene expression in fat, muscle, and liver, however, did not provide support for the functional involvement of these differences. In summary, the investigated RNO20 segment contains 1 or more gene variants that affect adiposity, glucose tolerance, serum leptin levels, and BP, but only when the animals are exposed to a particular environment, ie, high-fat-diet feeding. Further studies are needed to identify genes mediating these effects. Considering current changes in our lifestyle involving an increased calorie and fat intake, we believe that gene-environment interactions, such as those described here, play an important role in the current epidemic of obesity and obesityassociated hypertension.

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“…45 No significant effect of the differential segment was found in some other studies, however. 28,46 …”

Section: Discussionmentioning

confidence: 99%

Section: Strainsmentioning

confidence: 99%

Segment of Rat Chromosome 20 Regulates Diet-Induced Augmentations in Adiposity, Glucose Intolerance, and Blood Pressure

et al. 2003

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“…22 In these cases, the cardiac mass phenotype may be acting as a surrogate for the pressure load. On the other hand, genetic loci for cardiac mass that are independent of the influence of blood pressure have been found on rat chromosomes 2, 20 3, 9 10, 23 12, 24,25 and 17.…”

Section: Discussionmentioning

confidence: 99%

Right Ventricular Hypertrophy Secondary to Pulmonary Hypertension Is Linked to Rat Chromosome 17

et al. 2001

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Background-Fischer 344 (F344) rats are relatively resistant to hypoxia-induced right ventricular (RV) hypertrophy compared with the Wistar-Kyoto (WKY) strain. These 2 strains were used to examine the genetic basis for the differential response. Methods and Results-Male F 2 offspring from an F344ϫWKY intercross were exposed to hypoxia (10% O 2 ) for 3 weeks, and pulmonary artery pressure and cardiac chamber weights were measured. Genomic DNA was screened by use of polymorphic microsatellite markers across the whole genome (excluding the sex chromosomes). A quantitative trait locus (QTL) for RV weight was identified on rat chromosome 17 (lod score 6.5) that accounted for 22% of the total variance of RV weight in the F 2 population and was independent of pulmonary artery pressure. The peak was centered over marker D17Rat41, close to Chrm3, with a 1-lod support interval of 5 cM. Comparison of homologous regions in mice and humans suggested that Ryr2, the cardiac isoform of the ryanodine receptor, colocalizes with our QTL. A panel of somatic cell hybrids and fluorescence in situ hybridization mapped Ryr2 close to the gene Chrm3 within our QTL.

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“…However, the mean blood pressure effect measured in these congenic rat strains was relatively small clearly indicating that the transferred regions do not contain major genes for hypertension of the spontaneously hypertensive SHR/SHRSP rats (2)(3)(4)(5)(6)(7)(8).…”

Section: Introductionmentioning

confidence: 95%

Phenotypic selection: A successful strategy to fix major genes of hypertension

1999

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SUMMARYHypertension is dominantly inherited in cross hybrids between hypertensive SHR/Mol and normotensive BB/OK rats. We used these cross hybrids for repeated backcrossing of selected hypertensive animals onto normotensive BB/OK rats to fix high blood pressure and to generate a hypertensive and diabetic BB/OK rat subline. After 8 backcrosses, the backcross parents were genetically analysed with the aid of 259 microsatellite markers to identify SHR genes causing blood pressure of 177 + 10 mmHg in this BB/OK rat subline. Loci on chromosomes 1, 14 and 18 showed longest heterozygosity. These loci might contain major genes of the SHR rat causing hypertension in this BB/OK rat subline. This classical strategy seems to be most suitable to fix major genes of hypertension in particular and complex traits in general and therefore to generate new animal models.

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Genetic isolation of a region of chromosome 8 that exerts major effects on blood pressure and cardiac mass in the spontaneously hypertensive rat.

Cited by 80 publications

References 23 publications

Segment of Rat Chromosome 20 Regulates Diet-Induced Augmentations in Adiposity, Glucose Intolerance, and Blood Pressure

Segment of Rat Chromosome 20 Regulates Diet-Induced Augmentations in Adiposity, Glucose Intolerance, and Blood Pressure

Right Ventricular Hypertrophy Secondary to Pulmonary Hypertension Is Linked to Rat Chromosome 17

Phenotypic selection: A successful strategy to fix major genes of hypertension

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