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Physiol. Rev. 80: 135-172, 2000;
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Physiological Reviews, Vol. 80, No. 1, January 2000, pp. 135-172
Copyright ©2000 by the American Physiological Society

Genetic Analysis of Inherited Hypertension in the Rat

John P. Rapp

Department of Physiology and Molecular Medicine, Medical College of Ohio, Toledo, Ohio

Rapp, John P. Genetic Analysis of Inherited Hypertension in the Rat. Physiol. Rev. 80: 135-172, 2000.Blood pressure is a quantitative trait that has a strong genetic component in humans and rats. Several selectively bred strains of rats with divergent blood pressures serve as an animal model for genetic dissection of the causes of inherited hypertension. The goal is to identify the genetic loci controlling blood pressure, i.e., the so-called quantitative trait loci (QTL). The theoretical basis for such genetic dissection and recent progress in understanding genetic hypertension are reviewed. The usual paradigm is to produce segregating populations derived from a hypertensive and normotensive strain and to seek linkage of blood pressure to genetic markers using recently developed statistical techniques for QTL analysis. This has yielded candidate QTL regions on almost every rat chromosome, and also some interactions between QTL have been defined. These statistically defined QTL regions are much too large to practice positional cloning to identify the genes involved. Most investigators are, therefore, fine mapping the QTL using congenic strains to substitute small segments of chromosome from one strain into another. Although impressive progress has been made, this process is slow due to the extensive breeding that is required. At this point, no blood pressure QTL have met stringent criteria for identification, but this should be an attainable goal given the recently developed genomic resources for the rat. Similar experiments are ongoing to look for genes that influence cardiac hypertrophy, stroke, and renal failure and that are independent of the genes for hypertension.




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J. B. J. Kwok, R. Kapoor, T. Gotoda, Y. Iwamoto, Y. Iizuka, N. Yamada, K. E. Isaacs, V. V. Kushwaha, W. B. Church, P. R. Schofield, et al.
A Missense Mutation in Kynurenine Aminotransferase-1 in Spontaneously Hypertensive Rats
J. Biol. Chem., September 20, 2002; 277(39): 35779 - 35782.
[Abstract] [Full Text] [PDF]

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 Physiol. GenomicsHome page
A. Alemayehu, L. Breen, D. Krenova, and M. P. Printz
Reciprocal rat chromosome 2 congenic strains reveal contrasting blood pressure and heart rate QTL
Physiol Genomics, September 3, 2002; 10(3): 199 - 210.
[Abstract] [Full Text] [PDF]

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 Hum Mol GenetHome page
M.-T. Bihoreau, N. Megel, J. H. Brown, B. Kranzlin, L. Crombez, Y. Tychinskaya, J. Broxholme, S. Kratz, V. Bergmann, S. Hoffman, et al.
Characterization of a major modifier locus for polycystic kidney disease (Modpkdr1) in the Han:SPRD(cy/+) rat in a region conserved with a mouse modifier locus for Alport syndrome
Hum. Mol. Genet., September 1, 2002; 11(18): 2165 - 2173.
[Abstract] [Full Text] [PDF]

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 HypertensionHome page
J.-R. Clemitson, J. R. Pratt, S. Frantz, S. Sacks, and N. J. Samani
Kidney Specificity of Rat Chromosome 1 Blood Pressure Quantitative Trait Locus Region
Hypertension, September 1, 2002; 40(3): 292 - 297.
[Abstract] [Full Text] [PDF]

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 Physiol. GenomicsHome page
F. Sugiyama, G. A. Churchill, R. Li, L. J. M. Libby, T. Carver, K.-I. Yagami, S. W. M. John, and B. Paigen
QTL associated with blood pressure, heart rate, and heart weight in CBA/CaJ and BALB/cJ mice
Physiol Genomics, July 12, 2002; 10(1): 5 - 12.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Renal Physiol.Home page
J. Titze, H. Krause, H. Hecht, P. Dietsch, J. Rittweger, R. Lang, K. A. Kirsch, and K. F. Hilgers
Reduced osmotically inactive Na storage capacity and hypertension in the Dahl model
Am J Physiol Renal Physiol, July 1, 2002; 283(1): F134 - F141.
[Abstract] [Full Text] [PDF]

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 HypertensionHome page
H. Zimdahl, T. Kreitler, C. Gosele, D. Ganten, and N. Hubner
Conserved Synteny in Rat and Mouse for a Blood Pressure QTL on Human Chromosome 17
Hypertension, June 1, 2002; 39(6): 1050 - 1052.
[Abstract] [Full Text] [PDF]

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 ChestHome page
G. D. Leikauf, M. T. Borchers, D. R. Prows, and L. G. Simpson
Mucin Apoprotein Expression in COPD*
Chest, May 1, 2002; 121 (2009): 166S - 182S.
[Abstract] [Full Text] [PDF]

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 HypertensionHome page
C. F. Deschepper, I. Boutin-Ganache, A. Zahabi, and Z. Jiang
In Search of Cardiovascular Candidate Genes: Interactions Between Phenotypes and Genotypes
Hypertension, February 1, 2002; 39(2): 332 - 336.
[Abstract] [Full Text] [PDF]

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 Nucleic Acids ResHome page
S. Twigger, J. Lu, M. Shimoyama, D. Chen, D. Pasko, H. Long, J. Ginster, C.-F. Chen, R. Nigam, A. Kwitek, et al.
Rat Genome Database (RGD): mapping disease onto the genome
Nucleic Acids Res., January 1, 2002; 30(1): 125 - 128.
[Abstract] [Full Text] [PDF]

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 Cold Spring Harb Symp Quant BiolHome page
R.J. ROMAN, A.W. COWLEY, A. GREENE, A.E. KWITEK, P.J. TONELLATO, and H.J. JACOB
Consomic Rats for the Identification of Genes and Pathways Underlying Cardiovascular Disease
Cold Spring Harb Symp Quant Biol, January 1, 2002; 67(0): 309 - 316.
[Abstract] [PDF]

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 ScienceHome page
M. Stoll, A. W. Cowley Jr., P. J. Tonellato, A. S. Greene, M. L. Kaldunski, R. J. Roman, P. Dumas, N. J. Schork, Z. Wang, and H. J. Jacob
A Genomic-Systems Biology Map for Cardiovascular Function
Science, November 23, 2001; 294(5547): 1723 - 1726.
[Abstract] [Full Text] [PDF]

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 HypertensionHome page
M. R. Garrett, X. Zhang, O. I. Dukhanina, A. Y. Deng, and J. P. Rapp
Two Linked Blood Pressure Quantitative Trait Loci on Chromosome 10 Defined by Dahl Rat Congenic Strains
Hypertension, October 1, 2001; 38(4): 779 - 785.
[Abstract] [Full Text] [PDF]

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 HypertensionHome page
R. Barnard, G. Kelly, S. O. Manzetti, and E. L. Harris
Neither the New Zealand Genetically Hypertensive Strain nor Dahl Salt-Sensitive Strain Has an A1079T Transversion in the {alpha}1 Isoform of the Na+,K+-ATPase Gene
Hypertension, October 1, 2001; 38(4): 786 - 792.
[Abstract] [Full Text] [PDF]

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 J. Physiol.Home page
J Chen, G M Feller, J C Barbato, S Periyasamy, Z-J Xie, L G Koch, J I Shapiro, and S L Britton
Cardiac performance in inbred rat genetic models of low and high running capacity
J. Physiol., September 1, 2001; 535(2): 611 - 617.
[Abstract] [Full Text] [PDF]

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 HypertensionHome page
S. Frantz, J.-R. Clemitson, M.-T. Bihoreau, D. Gauguier, and N. J. Samani
Genetic Dissection of Region Around the Sa Gene on Rat Chromosome 1: Evidence for Multiple Loci Affecting Blood Pressure
Hypertension, August 1, 2001; 38(2): 216 - 221.
[Abstract] [Full Text] [PDF]

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 Physiol. GenomicsHome page
J. ZICHA, C. D. NEGRIN, Z. DOBESOVA, F. CARR, M. VOKURKOVA, M. W. MCBRIDE, J. KUNES, and A. F. DOMINICZAK
Altered Na+-K+ pump activity and plasma lipids in salt-hypertensive Dahl rats: relationship to Atp1a1 gene
Physiol Genomics, July 17, 2001; 6(2): 99 - 104.
[Abstract] [Full Text] [PDF]

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 Circ. Res.Home page
C. F. Deschepper, S. Masciotra, A. Zahabi, I. Boutin-Ganache, S. Picard, and T. L. Reudelhuber
Functional Alterations of the Nppa Promoter Are Linked to Cardiac Ventricular Hypertrophy in WKY/WKHA Rat Crosses
Circ. Res., February 2, 2001; 88(2): 223 - 228.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
B. K. Taylor, R. E. Roderick, E. St. Lezin, and A. I. Basbaum
Hypoalgesia and hyperalgesia with inherited hypertension in the rat
Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2001; 280(2): R345 - R354.
[Abstract] [Full Text] [PDF]

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 HypertensionHome page
C. D. Negrin, M. W. McBride, H. V. O. Carswell, D. Graham, F. J. Carr, J. S. Clark, B. Jeffs, N. H. Anderson, I. M. Macrae, and A. F. Dominiczak
Reciprocal Consomic Strains to Evaluate Y Chromosome Effects
Hypertension, February 1, 2001; 37(2): 391 - 397.
[Abstract] [Full Text] [PDF]

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 HypertensionHome page
A. W. Cowley Jr, R. J. Roman, M. L. Kaldunski, P. Dumas, J. G. Dickhout, A. S. Greene, and H. J. Jacob
Brown Norway Chromosome 13 Confers Protection From High Salt to Consomic Dahl S Rat
Hypertension, February 1, 2001; 37(2): 456 - 461.
[Abstract] [Full Text] [PDF]

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 Physiol. GenomicsHome page
Y. SAAD, M. R. GARRETT, and J. P. RAPP
Multiple blood pressure QTL on rat chromosome 1 defined by Dahl rat congenic strains
Physiol Genomics, January 19, 2001; 4(3): 201 - 214.
[Abstract] [Full Text] [PDF]

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 Hum Mol GenetHome page
C. L. Glenn, W. Y.S. Wang, A. V. Benjafield, and B. J. Morris
Linkage and association of tumor necrosis factor receptor 2 locus with hypertension, hypercholesterolemia and plasma shed receptor
Hum. Mol. Genet., August 12, 2000; 9(13): 1943 - 1949.
[Abstract] [Full Text] [PDF]

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 Physiol. GenomicsHome page
M. R. GARRETT, Y. SAAD, H. DENE, and J. P. RAPP
Blood pressure QTL that differentiate Dahl salt-sensitive and spontaneously hypertensive rats
Physiol Genomics, June 29, 2000; 3(1): 33 - 38.
[Abstract] [Full Text] [PDF]

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 Physiol. GenomicsHome page
A. W. COWLEY JR., M. STOLL, A. S. GREENE, M. L. KALDUNSKI, R. J. ROMAN, P. J. TONELLATO, N. J. SCHORK, P. DUMAS, and H. J. JACOB
Genetically defined risk of salt sensitivity in an intercross of Brown Norway and Dahl S rats
Physiol Genomics, April 27, 2000; 2(3): 107 - 115.
[Abstract] [Full Text] [PDF]

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 Physiol. GenomicsHome page
A. P. Provoost, M. Shiozawa, R. P. E. Van Dokkum, and H. J. Jacob
Transfer of the Rf-1 region from FHH onto the ACI background increases susceptibility to renal impairment
Physiol Genomics, February 28, 2002; 8(2): 123 - 129.
[Abstract] [Full Text] [PDF]

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 Physiol. GenomicsHome page
M. LO, K. L. LIU, J.-R. CLEMITSON, J. SASSARD, and N. J. SAMANI
Chromosome 1 blood pressure QTL region influences renal function curve and salt sensitivity in SHR
Physiol Genomics, February 11, 2002; 8(1): 15 - 21.
[Abstract] [Full Text] [PDF]

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 Physiol. GenomicsHome page
M. R. Garrett and J. P. Rapp
Two closely linked interactive blood pressure QTL on rat chromosome 5 defined using congenic Dahl rats
Physiol Genomics, February 28, 2002; 8(2): 81 - 86.
[Abstract] [Full Text] [PDF]

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 Physiol. GenomicsHome page
M. Liang, B. Yuan, E. Rute, A. S. Greene, A.-P. Zou, P. Soares, G. D. MCQuestion, G. R. Slocum, H. J. Jacob, and A. W. Cowley Jr.
Renal medullary genes in salt-sensitive hypertension: a chromosomal substitution and cDNA microarray study
Physiol Genomics, February 28, 2002; 8(2): 139 - 149.
[Abstract] [Full Text] [PDF]

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 CirculationHome page
M. Suzuki, K. M. Carlson, D. A. Marchuk, and H. A. Rockman
Genetic Modifier Loci Affecting Survival and Cardiac Function in Murine Dilated Cardiomyopathy
Circulation, April 16, 2002; 105(15): 1824 - 1829.
[Abstract] [Full Text] [PDF]


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