Biological variability in Wistar-Kyoto rats. Implications for research with the spontaneously hypertensive rat.

The spontaneously hypertensive rat (SHR) initially bred in Kyoto is the most widely studied animal model of essential hypertension. As controls for the SHR, most workers have used normotensive descendants of Wistar rats from the colony in Kyoto from which the SHR strain was derived (Wistar-Kyoto rats, WKY). But the presumption that WKY are serviceable controls for SHR rests on the tacit assumption that all WKY constitute a single inbred strain. It appears, however, that whereas the National Institutes of Health distributed breeding stocks of SHR after they had been fully inbred (i.e., after 20 generations of brother-sister mating), the breeding stocks of WKY were distributed before they had been fully inbred. Accordingly, the biological variability of WKY may be greater than that of SHR. To investigate this possibility, we obtained SHR and WKY from two of the largest commercial suppliers in the United States and systematically measured the growth rate and blood pressure of these rats under identical physical and metabolic conditions. We found that WKY from one source differed from those of the other in both growth rate and blood pressure. In contrast, the SHR from the two suppliers were not different with respect to either growth rate or blood pressure. Because the National Institutes of Health may have distributed breeding stocks of WKY as early as the F6 generation, it is possible that rats currently designated as WKY do not constitute a single inbred strain. Thus, interpretation of studies employing "the Wistar-Kyoto rat strain" as a control for the SHR may be much more problematic than has previously been recognized.