title: Normotension in Lewis and Dahl salt-resistant rats is governed by different genes.
abstract: OBJECTIVE
  Inbred rodent models simulating essential hypertension and normotension are useful tools in discovering genes controlling blood pressure (BP) homeostasis. An analysis of a F2 population made from crosses of hypertensive Dahl salt-sensitive (DSS) and normotensive Lewis rats did not detect a BP quantitative trait locus (QTL) on chromosome 7 (Chr 7). However, false negativity could not be excluded. If a BP QTL could be proven to exist, what gene(s) may be responsible for this QTL.
  
  
  METHODS
  We first constructed reciprocal congenic strains for a Chr 7 segment and determined functional domains of prominent candidate genes.
  
  
  RESULTS
  A congenic strain made in the DSS rat background exhibited a BP effect, indicating that a BP QTL, C7QTL, inhabits Chr 7. Contrarily, a congenic strain constructed in the Lewis rat background did not change BP, demonstrating a dependence of C7QTL on the DSS rats environment. Among the candidate genes, tachykinin 2 (Tac2), neurexophilin 4 (Nxph4) and retinol dehydrogenase 2 (Rdh2) bear nonsynonymous changes comparing DSS and Lewis rats, but are the same comparing DSS and Dahl salt-resistant (DSR) rats. In contrast, the Lewis alleles of 11-beta-hydroxylase (Cyp11b1), aldosterone synthase (Cyp11b2) and Cytochrome P-450 11B3 (Cyp11b3) are identical to those of DSS rats, but different from those of DSR rats.
  
  
  CONCLUSIONS
  Thus, the failure to detect a linkage between a Chr 7 segment and BP in F2(DSS × Lewis) can be attributed to false negativity. Tac2, Nxph4 and Rdh2 are priority candidate genes for C7QTL. Lewis and DSR rats are both normotensive, but their underlying genetic determinants are different.
authors.affiliation: Research Centre, Centre Hospitalier de l'Université de Montréal, Université de Montréal, Montreal, Quebec, Canada.
authors.forename: Kimberley
authors.initials: K
authors.lastname: Crespo
authors.forename: Cristina
authors.initials: C
authors.lastname: Chauvet
authors.forename: Marilyne
authors.initials: M
authors.lastname: Blain
authors.forename: Annie
authors.initials: A
authors.lastname: Ménard
authors.forename: Julie
authors.initials: J
authors.lastname: Roy
authors.forename: Alan Y
authors.initials: AY
authors.lastname: Deng
mesh_terms: D000429:Alcohol Oxidoreductases / Q000235:genetics; D000818:Animals; D001794:Blood Pressure; D019405:Cytochrome P-450 CYP11B2 / Q000235:genetics; D006023:Glycoproteins / Q000235:genetics; D006973:Hypertension / Q000235:genetics*; D008297:Male; D009479:Neuropeptides / Q000235:genetics; D040641:Quantitative Trait Loci; D051381:Rats; D020303:Rats, Inbred Dahl; D011917:Rats, Inbred Lew; D013252:Steroid 11-beta-Hydroxylase / Q000235:genetics; D015320:Tachykinins / Q000235:genetics
chemical_list: D006023:Glycoproteins; D009479:Neuropeptides; D015320:Tachykinins; C112162:neurexophilin; D000429:Alcohol Oxidoreductases; C022520:retinol dehydrogenase; C120361:Cyp11b3 protein, rat; D019405:Cytochrome P-450 CYP11B2; D013252:Steroid 11-beta-Hydroxylase