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Am J Physiol Renal Physiol (July 23, 2008). doi:10.1152/ajprenal.90341.2008
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Submitted on June 2, 2008
Revised on July 3, 2008
Accepted on July 21, 2008

CHROMOSOME SUBSTITUTION REVEALS THE GENETIC BASIS OF DAHL SALT-SENSITIVE HYPERTENSION AND RENAL DISEASE

David L. Mattson1*, Melinda R Dwinell1, Andrew S Greene1, Anne E Kwitek2, Richard J. Roman1, Howard J Jacob, and Allen W. Cowley Jr.1

1 Medical College of Wisconsin
2 University of Iowa

* To whom correspondence should be addressed. E-mail: dmattson{at}mcw.edu.

This study examined the genetic basis of hypertension and renal disease in Dahl SS/Mcwi (Dahl Salt-Sensitive) rats using a complete chromosome substitution panel of consomic rats in which each of the 20 autosomes and the X and Y chromosomes were individually transferred from the BN (Brown Norway) rat onto the Dahl SS/Mcwi genetic background. Male and female rats of each of the two parental and 22 consomic strains (10-12 rats/group) were fed a high salt (8.0% NaCl) diet for 3 weeks. Mean arterial blood pressure (MAP) rose by 60 mmHg and urinary protein and albumin excretion increased 3 and 20 fold, respectively, in male SS/Mcwi rats compared to BN controls. Substitution of chromosomes 1, 5, 7, 8, 13, or 18 from the BN onto the SS/Mcwi background attenuated the development of hypertension, proteinuria and albuminuria in male rats. In female rats, substitution of chromosomes 1 and 5 also decreased blood pressure, protein excretion, and albumin excretion. These studies also identified several chromosomes in male (6,11, Y) and female rats (4,6,11,19,20) that reduced albuminuria without altering blood pressure. These data indicate that genes contributing to salt-sensitive hypertension are found on multiple chromosomes of the Dahl SS/Mcwi rat. Furthermore, this consomic rat panel provides a stable genetic platform that can facilitate further gene mapping by either linkage studies or the breeding of congenic and subcongenic rats.




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J. H. Wiessner, M. R. Garrett, R. J. Roman, and N. S. Mandel
Dissecting the genetic basis of kidney tubule response to hyperoxaluria using chromosome substitution strains
Am J Physiol Renal Physiol, August 1, 2009; 297(2): F301 - F306.
[Abstract] [Full Text] [PDF]




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