Genetic Characterization of the ‘New’ Harlan Sprague Dawley Dahl Salt-Sensitive Rats

Abstract

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 these 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 <.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 <.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.