(Hypertension. 1997;30:854-858.)
© 1997 American Heart Association, Inc.
Articles |
Genetic Isolation of a Chromosome 1 Region Affecting Blood Pressure in the Spontaneously Hypertensive Rat
From the Department of Laboratory Medicine (E. St. L., W.L., J.-M.W., N.W.) and the Animal Care Facility (D.L.), University of California, San Francisco; the Institute of Biology, 1st Medical Faculty, Charles University (V.K., D.K., M.P.), and the Institute of Physiology, Czech Academy of Sciences (V.K., A.M., M.Z., V.Z., M.P.), Prague, Czech Republic.
Abstract Recent linkage studies in the spontaneously hypertensive rat (SHR) suggest that a blood pressure regulatory gene or genes may be located on rat chromosome 1q. To investigate this possibility, we replaced a region 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 transferred BN chromosome segment, 24-hour average systolic and diastolic blood pressures were significantly lower than in male progenitor SHR. Polymerase chain reaction genotyping using 60 polymorphic microsatellite markers dispersed throughout the genome confirmed the congenic status of the new strain designated SHR.BN-D1Mit3/Igf2. These findings provide direct evidence that a blood pressure regulatory gene exists on the differential segment of chromosome 1 that is sufficient to decrease blood pressure in the SHR. The SHR.BN-D1Mit3/Igf2 congenic strain represents an important new model for fine mapping and characterization of genes on chromosome 1 involved in the pathogenesis of spontaneous hypertension.
Key Words: hypertension, genetic • congenic strain • trait locus • genes
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