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The use of designer rats in the genetic dissection of hypertension

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Abstract

The rat is a well-established model for hypertension research, in both physiologic and pharmacologic study. Quantitative trait loci (QTL) for blood pressure and related phenotypes have been described on every rat chromosome; therefore, more simplified models must be generated to identify and study the function of the gene(s) located by QTL analysis. Designer rat strains, such as congenic and consomic strains, which share phenotypic and genotypic characteristics with humans but with a greatly simplified genetic background, would yield a powerful platform for functional studies, especially when combined with microarray technologies. Development of these designer rats would result in better-defined disease models that can be used in physiologic and applied pharmacologic studies to better treat human essential hypertension.

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References and Recommended Reading

  1. Ward R: Familial aggregation and genetic epidemiology of blood pressure. In Hypertension: Pathophysiology, Diagnosis and Management. Edited by Laragh JH, Brenner BM. New York: Raven Press; 1990:81–100.

    Google Scholar 

  2. Hamet P, Pausova Z, Adarichev V, et al.: Hypertension: genes and environment. J Hypertens 1998, 16:397–418.

    Article  PubMed  CAS  Google Scholar 

  3. Dominiczak A, Negrin DC, Clark JS, et al.: Genes and hypertension: from gene mapping in experimental models to vascular gene transfer strategies. Hypertension 2000, 35:164–172. Good review of current rat resources.

    PubMed  CAS  Google Scholar 

  4. Simon D, Karet FE, Hamdan JM, et al.: Bartter‘s syndrome, hypokalaemic alkalosis with hypercalciuria, is caused by mutations in the Na-K-2Cl cotransporter NKCC2. Nature Genet 1996, 13:183–188.

    Article  PubMed  CAS  Google Scholar 

  5. Simon D, Karet FE, Rodriguez-Soriano J, et al.: Genetic heterogeneity of Bartter‘s syndrome revealed by mutations in the K+ channel, ROMK. Nature Genet 1996, 14:152–156.

    Article  PubMed  CAS  Google Scholar 

  6. Shimkets RA, Warnock DG, Bositis CM, et al.: Liddle‘s syndrome: heritable human hypertension caused by mutations in the B subunit of the epithelial sodium channel. Cell 1994, 79:407–414.

    Article  PubMed  CAS  Google Scholar 

  7. Casari G, Barlassina C, Cusi D, et al.: Association of the alpha-adducin locus with essential hypertension. Hypertension 1995, 25:320–326.

    PubMed  CAS  Google Scholar 

  8. Jeunemaitre X, Soubrier F, Kotelevtsev YV, et al.: Molecular basis of human hypertension: role of angiotensinogen. Cell 1992, 71:169–180.

    Article  PubMed  CAS  Google Scholar 

  9. Jeunemaitre X, Lifton RP, Hunt SC, et al.: Absence of linkage between the angiotensin converting enzyme locus and human essential hypertension. Nature Genet 1992, 1:72–75.

    Article  PubMed  CAS  Google Scholar 

  10. Harrap S, Davidson HR, Conor JM, et al.: The angiotensin I-converting enzyme gene and predisposition to high blood pressure in man. Hypertension 1993, 21:455–460.

    PubMed  CAS  Google Scholar 

  11. Iwai N, Ohmichi N, Hanai K, et al.: Human SA gene locus as a candidate locus for essential hypertension. Hypertension 1994, 23:375–380.

    PubMed  CAS  Google Scholar 

  12. Kato N, Sugiyama T, Tabika T, et al.: Lack of association between alpha-adducin locus and essential hypertension in the Japanese population. Hypertension 1998, 31:730–733.

    PubMed  CAS  Google Scholar 

  13. Brand E, Chatelain N, Keavney B, et al.: Evaluation of the angiotensinogen locus in human essential hypertension. Hypertension 1998, 31:735–739.

    Google Scholar 

  14. Niu T, Xu X, Rogos J, et al.: Angiotensinogen gene and hypertension in Chinese. J Clin Invest 1998, 101:188–194.

    Article  PubMed  CAS  Google Scholar 

  15. Julier C, Delepine M, Keavney B, et al.: Genetic susceptibility for human familial essential hypertension in a region of homology with blood pressure linkage on rat chromosome 10. Human Molec Genet 1997, 6:2077–2085.

    Article  CAS  Google Scholar 

  16. Krushkal J, Xiong M, Ferrell R, et al.: Linkage and association of adrenergic and dopamine receptor genes in the distal portion of the long arm of chromosome 5 with systolic blood pressure variation. Human Molec Genet 1998, 7:1379–1383.

    Article  CAS  Google Scholar 

  17. Mansfield TA, Simon DB, Farfel Z, et al.: Multilocus linkage of familial hyperkalaemia and hypertension, pseudohypoaldosteronism type II, to chromosomes 1q31-42 and 17p11-q21. Nature Genet 1997, 16:202–205.

    Article  PubMed  CAS  Google Scholar 

  18. Rapp J: Genetic analysis of inherited hypertension in the rat. Physiol Rev 2000, 80:135–172. Very thorough review of the rat models for hypertension as well as basic background information on linkage.

    PubMed  CAS  Google Scholar 

  19. Stoll M, Kwitek-Black AE, Cowley AW Jr, et al.: New target regions for human hypertension via comparative genomics. Genome Res 2000, 10:473–482.

    Article  PubMed  CAS  Google Scholar 

  20. Snell G: Methods for study of histocompatibility genes. J Genet 1948, 49:87–108.

    Article  PubMed  CAS  Google Scholar 

  21. Markel PS, Ebeling C, Carlson GA, et al.: Theoretical and empirical issues for marker-assisted breeding of congenic mouse strains. Nature Genet 1997, 17:292–297. This paper describes the speed congenic approach.

    Article  Google Scholar 

  22. Wakeland E, Morel L, Achey K, et al.: Speed congenics: a classic technique in the fast lane (relatively speaking). Immunol Today 1997, 18:472–477. This paper also describes the speed congenic approach.

    Article  PubMed  CAS  Google Scholar 

  23. Zhang Q, Dene H, Jacob H, et al.: Interval mapping and congenic strains for a blood pressure QTL on rat chromosome 13. Mammalian Genome 1997, 9:636–641.

    Article  Google Scholar 

  24. St Lezin E, Griffin KA, Picken M, et al.: Genetic isoloation of a chromosome 1 region affecting susceptibility to hypertension-induced renal damage in the spontaneously hypertensive rat. Hypertension 1999, 34:187–191.

    Google Scholar 

  25. Jiang J, Stec DE, Drummond H, et al.: Transfer of a saltresistant renin allele raises blood pressure in Dahl saltsensitive rats. Hypertension 1997, 29:619–627.

    PubMed  CAS  Google Scholar 

  26. Cowley A, Roman RR, Kaldunski ML, et al.: Transfer of brown Norway rat chromosome 13 into Dahl S genomic background confers protection from high salt diet [abstract P132]. Hypertension 2000, 36:717.

    Google Scholar 

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Kwitek-Black, A.E., Jacob, H.J. The use of designer rats in the genetic dissection of hypertension. Current Science Inc 3, 12–18 (2001). https://doi.org/10.1007/s11906-001-0072-0

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