Genetic Analysis of Blood Pressure in Spontaneously Hypertensive Rats

Tanase, Hisao; Suzuki, Yoshio; Ooshima, Akira; Yamori, Yukio; Okamoto, Kozo

doi:10.1253/jcj.34.1197

Cited by 97 publications

(41 citation statements)

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“…In previous biometric genetic studies of hypertension, such heteroscedasticity has been attributed to environment-genotype interaction. 12 The mean arterial pressures of the F 2 generations were similar to those of the F] generations with the variance of each F 2 generation (VF 2 ) being greater than that of the corresponding F[ (VF,). Because VF, is determined by environmental factors and VF 2 is determined by genetic and environmental factors, we estimated the degree of genetic determination of blood pressure from the formula 18 : VF 2 In both experiments, the degree of genetic determination of blood pressure was approximately 60% even though different normotensive strains were used, and the measurements of blood pressure were obtained at different times of the day and in different sexes.…”

Section: Biometric Genetic Analysismentioning

confidence: 75%

“…In several studies in which SHR have been crossed with normotensive rats, it has been reported that blood pressure follows a simple additive mode of inheritance and that the hypertension is primarily determined by a single major locus. 6 " 8 In other studies, hypertension has not been transmitted in a simple additive Mendelian fashion, and dominance effects of alleles that de-crease blood pressure have been evident. 9 Some investigators have also reported data consistent with complex epistatic effects of the genes that regulate blood pressure.…”

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confidence: 97%

“…9 Some investigators have also reported data consistent with complex epistatic effects of the genes that regulate blood pressure. 10 - 12 Such differing results might stem from the fact that a variety of normotensive rats with differing genetic backgrounds have been used in the classical crosses with the SHR. Yet variable results have also been reported in studies in which normotensive rats of apparently similar genetic background have been used.…”

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Biometric genetic analysis of blood pressure in the spontaneously hypertensive rat.

et al. 1990

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The spontaneously hypertensive rat is the most widely studied animal model of essential hypertension, yet the genetics of transmission of high blood pressure in this strain have not been clearly defined. It has been proposed that in the spontaneously hypertensive rat, blood pressure follows a simple additive mode of inheritance and that the hypertension is primarily determined by a single major locus. To investigate the genetics of transmission of increased blood pressure in the spontaneously hypertensive rat, we performed a biometric genetic analysis of multiple, direct measurements of arterial pressure in unanesthetized, unrestrained rats derived by crossing spontaneously hypertensive rats with two different inbred normotensive strains, the Charles River Wistar-Kyoto rat and the Lewis rat In both crosses, approximately 60% of the variation in blood pressure could be assigned to genotypic variation. The data fit an additive-dominance model of inheritance in which alleles decreasing blood pressure were partially dominant Thus, in offspring derived from crosses between spontaneously hypertensive rats and Wistar-Kyoto rats or spontaneously hypertensive rats and Lewis rats that are raised under ordinary laboratory conditions, increased blood pressure is not determined by simple additive effects of alleles at a single major locus. The current findings are consistent with the possibility that in the spontaneously hypertensive rat, hypertension may arise from mutations in alleles that ordinarily act in a dominant fashion to suppress blood pressure. {Hypertension 1990;16:718-724)

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Section: Biometric Genetic Analysismentioning

confidence: 75%

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confidence: 97%

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confidence: 99%

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Biometric genetic analysis of blood pressure in the spontaneously hypertensive rat.

et al. 1990

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“…The initial process of development of SHR as well as a classical segregation study by Tanase et al 52 suggested that only a limited number of genetic loci (or QTLs) were involved in hypertension in SHR. 45 This observation implies that the appropriate combination of several genomic regions of SHR/SHRSP can 'reconstruct' hypertension on the WKY background to some extent.…”

Section: Role Of Genetic Analysis Of Shr and Shrsp In The Post-gwas Eramentioning

confidence: 99%

The stroke-prone spontaneously hypertensive rat: still a useful model for post-GWAS genetic studies?

et al. 2012

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The stroke-prone spontaneously hypertensive rat (SHRSP) is a unique genetic model of severe hypertension and cerebral stroke. SHRSP, as well as the spontaneously hypertensive rat, the parental strain of SHRSP, has made a tremendous contribution to cardiovascular research. However, the genetic mechanisms underlying hypertension and stroke in these rats have not yet been clarified. Recent studies using whole-genome sequencing and comprehensive gene expression analyses combined with classical quantitative trait loci analyses provided several candidate genes, such as Ephx2, Gstm1 and Slc34a1, which still need further evidence to define their pathological roles. Currently, genome-wide association studies can directly identify candidate genes for hypertension in the human genome. Thus, genetic studies in SHRSP and other rat models must be focused on the pathogenetic roles of 'networks of interacting genes' in hypertension, instead of searching for individual candidate genes. Keywords: cerebral stroke; genetics; hypertension; QTL; SHRSP INTRODUCTIONThe stroke-prone spontaneously hypertensive rat (SHRSP) is a unique genetic model of severe hypertension and cerebral stroke. Two decades have passed since the first pioneering studies on quantitative trait loci (QTLs) of blood pressure (BP) in SHRSP. 1,2 In spite of all efforts, the genetic mechanisms underlying hypertension or cerebral stroke in this rat model remain unknown. During this period, genetic analyses in humans have progressed dramatically. Technologies have made it possible to genotype a large number of samples and analyze an enormous amount of single-nucleotide polymorphism data. Genome-wide association studies (GWAS) that rely on such advanced technologies have revealed a number of loci associated with increased BP in humans. [3][4][5][6][7][8][9][10] Under such circumstance, what is the role of SHRSP and other models in genetic studies of cardiovascular diseases? In this review, we will address this issue and summarize the genetic studies performed thus far in SHRSP.

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“…9 " 15 Selective breeding for high or low blood pressure concentrates in the respective strains the genes for high or low blood pressure which happen to be segregating in the base population. Figure 1 shows diagramatically that selective breeding separates high and low selected lines from the extremes of the base population.…”

Section: Polygenic Inheritance Of Blood Pressurementioning

confidence: 99%

A paradigm for identification of primary genetic causes of hypertension in rats.

Rapp¹

1983

Hypertension

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A paradigm is developed for identifying the genes (and the biochemical-physiological traits for which the genes code) that cause differences in blood pressure in inbred strains of rats. A biochemical-physiological trait which meets the following four criteria is one which can reasonably be accepted as causing genetic differences in blood pressure: 1) a difference in a biochemical or physiological trait between two strains must be demonstrated; 2) the trait must be shown to follow Mendelian inheritance; 3) the genes identified in criterion 2 must co-segregate with an increment in blood pressure which is significantly different from zero; and 4) there must be some logical biochemical and/or physiological link between the trait and blood pressure. Traits which do not show discrete phenotypes following Mendelian inheritance may correlate with blood pressure in segregating populations. In this case no rigorous cause and effect genetic argument is possible because such correlations could arise from complex primary genetic causes or as secondary effects of blood pressure on the biochemical-physiological trait.

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Genetic Analysis of Blood Pressure in Spontaneously Hypertensive Rats

Cited by 97 publications

References 28 publications

Biometric genetic analysis of blood pressure in the spontaneously hypertensive rat.

Biometric genetic analysis of blood pressure in the spontaneously hypertensive rat.

The stroke-prone spontaneously hypertensive rat: still a useful model for post-GWAS genetic studies?

A paradigm for identification of primary genetic causes of hypertension in rats.

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