RECIPROCAL CONGENIC LINES FOR A MAJOR RECIPROCAL CONGENIC LINES FOR A MAJOR RECIPROCAL CONGENIC LINES FOR A MAJOR RECIPROCAL CONGENIC LINES FOR A MAJOR

ABSTRACT 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) spontaneous hypertensive rat genome and vice versa. The phenotype was the latency to develop stroke under a Japanese high-salt, low-potassium diet for 3 months (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 to 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 month 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. Keywords: stroke, genetics, QTL, congenic lines, functional genomics