title: Genetic characterization of the "new" Harlan Sprague Dawley Dahl salt-sensitive rats.
abstract: In 1994, it was reported that Dahl salt-sensitive SS/Jr rats supplied by Harlan Sprague Dawley were genetically contaminated and resistant to the pressor effects of a high salt diet. Harlan Sprague Dawley subsequently developed new pedigree expansion and production colonies from their foundation colony to supply new, purportedly inbred, Harlan Sprague Dawley SS/Jr (S(HSD)). To evaluate the genetic integrity and salt sensitivity of thse new S(HSD), we performed genotyping (microsatellite DNA markers) and phenotyping (radiotelemetric arterial pressure) of 12 S(HSD), 16 "authentic" SS/Jr from the inbred colony of John Rapp (S(Rapp)), 9 Harlan Sprague Dawley salt-resistant SR/Jr (R(HSD)), and (genotyping only) 6 known "contaminated" Harlan Sprague Dawley Dahl SS/Jr (S*). In the genotyping studies, 20 of 22 markers revealed polymorphisms between S(Rapp) and S* and 18 were polymorphic between S(Rapp) and R(Rapp), but none of the 22 markers revealed polymorphisms between S(Rapp) and the new S(HSD). The phenotyping studies showed that during an ultra-low salt diet, mean arterial pressure was higher (P < .05) in both authentic S(Rapp) (129 +/- 2 mm Hg; mean +/- SE) and new S(HSD) (120 +/- 2 mm Hg) than in R(HSD) (93 +/- 1 mm Hg). A high salt diet increased mean arterial pressure in every S(HSD) and S(Rapp). Increases in mean arterial pressure after 4 weeks of a high salt diet were significantly (P < 0.05) greater in authentic S(Rapp) (+51 +/- 3 mm Hg) than in new S(HSD) (+39 +/- 3 mm Hg). In addition, salt-induced mortality was significantly greater in S(Rapp) (62.5%) than S(HSD) (8.3%) after 8 weeks (P < 0.01). S(HSD) were genotypically indistinguishable from S(Rapp), had an elevated arterial pressure on a low salt diet, and had a pressor response to salt. Thus, the new S(HSD) supplied to us had several characteristics of inbred Dahl SS/Jr and did not have evidence of the previously detected genetic contamination. However, phenotypic characteristics such as body weight, salt-induced hypertension, and mortality were significantly different in S(HSD) compared with S(Rapp). This may reflect genetic differences between these two strains or differences in environmental factors and suggests that the S(HSD) and S(Rapp) may now constitute distinct substrains of Dahl SS/Jr.
authors.affiliation: Hypertension Specialized Center of Research, College of Medicine, University of Iowa, Iowa City 52242-1101, USA.
authors.forename: R Y
authors.initials: RY
authors.lastname: Walder
authors.forename: D A
authors.initials: DA
authors.lastname: Morgan
authors.forename: W G
authors.initials: WG
authors.lastname: Haynes
authors.forename: R D
authors.initials: RD
authors.lastname: Sigmund
authors.forename: A M
authors.initials: AM
authors.lastname: McClain
authors.forename: J B
authors.initials: JB
authors.lastname: Stokes
authors.forename: A L
authors.initials: AL
authors.lastname: Mark
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000235:genetics*; D005260:Female; D005838:Genotype; D008297:Male; D010641:Phenotype; D051381:Rats; D017207:Rats, Sprague-Dawley / Q000235:genetics*; D012982:Sodium, Dietary / Q000008:administration & dosage*
chemical_list: D012982:Sodium, Dietary