Reciprocal congenic lines for a major stroke QTL on rat chromosome 1

We previously identified a quantitative trait locus (QTL) for stroke proneness between the kallikrein ( Klk) and Mt1pa markers on rat chromosome 1. To gain functional insights, we constructed congenic strains by introgressing either the whole or selected chromosomal segments from the stroke-prone (SHRsp) onto the stroke-resistant (SHRsr) spontaneously hypertensive rat genome and vice versa. The phenotype was the latency to develop stroke under a Japanese high-salt, low-potassium diet for 3 mo [known as Japanese diet (JD)]. Blood pressure (BP) was measured by tail cuff throughout the experiment. Urinary protein excretion was monitored in all lines under JD. The SHRsp-derived lines carrying the SHRsr allele, and particularly the D1Rat134- Mt1pa chromosomal segment, had a significant delay of stroke occurrence and improved survival compared with SHRsp ( P < 0.001). On the other hand, a significant occurrence of stroke events (20%) was detected in the reciprocal lines by the end of the 3-mo treatment with JD ( P = 0.003). The stroke phenotype was also associated with increased proteinuria. Our results underscore the functional importance of the Chr 1 stroke QTL. Furthermore, they underscore the utility of stroke/congenic lines in dissecting the genetics of stroke.