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(Hypertension. 1999;34:187-191.)
© 1999 American Heart Association, Inc.

Scientific Contributions

Genetic Isolation of a Chromosome 1 Region Affecting Susceptibility to Hypertension-Induced Renal Damage in the Spontaneously Hypertensive Rat

Elizabeth St. Lezin; Karen A. Griffin; Maria Picken; Monique C. Churchill; Paul C. Churchill; Theodore W. Kurtz; Weizhong Liu; Ning Wang; Vladimir Kren; Vaclav Zidek; Michal Pravenec; Anil K. Bidani

From the Department of Laboratory Medicine, University of California (E.S.L., T.W.K., W.L., N.W.), San Francisco, Calif; Departments of Internal Medicine and Pathology, Loyola University and Hines Veterans Administration Hospital (K.A.G., M.P., A.K.B.), Maywood, Ill; Department of Physiology, Wayne State University School of Medicine (M.C.C., P.C.C.), Detroit, Mich; Institute of Physiology, Czech Academy of Sciences (V.K., V.Z., M.P.), Prague, Czech Republic; and Institute of Biology and Medical Genetics, 1st Medical Faculty, Charles University (V.K., M.P.), Prague, Czech Republic.

Correspondence to Elizabeth St. Lezin, MD, Department of Laboratory Medicine, University of California, San Francisco/Mt. Zion Medical Center, 1600 Divisadero St, San Francisco, CA 94143-1613. E-mail stlezin{at}pangloss.ucsf.edu

Abstract—Linkage studies in the fawn-hooded hypertensive rat have suggested that genes influencing susceptibility to hypertension-associated renal failure may exist on rat chromosome 1q. To investigate this possibility in a widely used model of hypertension, the spontaneously hypertensive rat (SHR), we compared susceptibility to hypertension-induced renal damage between an SHR progenitor strain and an SHR congenic strain that is genetically identical except for a defined region of chromosome 1q. Backcross breeding with selection for the markers D1Mit3 and Igf2 on chromosome 1 was used to create the congenic strain (designated SHR.BN-D1Mit3/Igf2) that carries a 22 cM segment of chromosome 1 transferred from the normotensive Brown Norway rat onto the SHR background. Systolic blood pressure (by radiotelemetry) and urine protein excretion were measured in the SHR progenitor and congenic strains before and after the induction of accelerated hypertension by administration of DOCA-salt. At the same level of DOCA-salt hypertension, the SHR.BN-D1Mit3/Igf2 congenic strain showed significantly greater proteinuria and histologically assessed renal vascular and glomerular injury than the SHR progenitor strain. These findings demonstrate that a gene or genes that influence susceptibility to hypertension-induced renal damage have been trapped in the differential chromosome segment of the SHR.BN-D1Mit3/Igf2 congenic strain. This congenic strain represents an important new model for the fine mapping of gene(s) on chromosome 1 that affect susceptibility to hypertension-induced renal injury in the rat.

Key Words: genetics • chromosome, rat, 1 • hypertension, renal

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