GENETIC ISOLATION OF A CHROMOSOME-1 REGION AFFECTING BLOOD-PRESSURE IN THE SPONTANEOUSLY HYPERTENSIVE RAT

Recent linkage studies in the spontaneously hypertensive rat (SHR) sug gest that a blood pressure regulatory gene or genes may be located on rat chromosome 1q. To investigate this possibility, we replaced a regi on of chromosome 1 in the SHR (defined by the markers D1Mit3 and Igf2) with the corresponding chromosome segment from the normotensive Brown -Norway (BN) strain. In male SHR congenic rats carrying the transferre d BN chromosome segment, 24-hour average systolic and diastolic blood pressures were significantly lower than in male progenitor SHR. Polyme rase chain reaction genotyping using 60 polymorphic microsatellite mar kers dispersed throughout the genome confirmed the congenic status of the new strain designated SHR.BN-D1Mit3/Igf2. These findings provide d irect evidence that a blood pressure regulatory gene exists on the dif ferential segment of chromosome 1 that is sufficient to decrease blood pressure in the SHR. The SHR.BN-D1Mit3/Igf2 congenic strain represent s an important new model for fine mapping and characterization of gene s on chromosome 1 involved in the pathogenesis of spontaneous hyperten sion.