Transfer of the Rf-1 region from FHH onto the ACI background increases susceptibility to renal impairment

• Published in: Physiological genomics Vol. 8; no. 2; pp. 123 - 129
• Main Authors: Provoost, Abraham P, Shiozawa, Masahide, Van Dokkum, Richard P. E, Jacob, Howard J
• Format: Journal Article
• Language: English
• Published: United States Am Physiological Soc 28.02.2002
• Subjects: Animals; Animals, Congenic; Blood Pressure - genetics; Crosses, Genetic; Female; Gene Transfer Techniques; Genetic Markers - genetics; Genetic Predisposition to Disease - genetics; Kidney Failure, Chronic - genetics; Kidney Failure, Chronic - physiopathology; Kidney Function Tests; Kidney Glomerulus - physiopathology; Male; Rats; Rats, Inbred ACI; Systole - genetics; Transgenes - genetics
• ISSN: 1094-8341; 1531-2267
• DOI: 10.1152/physiolgenomics.00030.2000

1 Department of Pediatric Surgery, Erasmus University, 3000 DR Rotterdam, The Netherlands 2 Laboratory for Genetics Research, Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226 The genetically hypertensive fawn-hooded (FHH/Eur) rat is characterized by the early presence of systolic and glomerular hypertension, progressive proteinuria (UPV), and albuminuria (UAV), and focal glomerulosclerosis, resulting in premature death from renal failure. Previous studies showed that at least five genetic loci ( Rf-1 to Rf-5 ) were linked to the development of renal impairment. Of these five, Rf-1 appears to play a major role. To study the impact of Rf-1 in the absence of the other loci, we transferred the Rf-1 region of chromosome 1, between the markers D1Mit34 and D1Rat156 , Rf-1B for short, onto the genomic background of the normotensive August x Copenhagen Irish (ACI) rat. In this congenic strain, named ACI.FHH- D1Mit34 / Rat156 or ACI.FHH- Rf1B , we challenged the renal hemodynamic function of these animals by studying the effects of unilateral nephrectomy (UNX) alone, or combined with N G -nitro- L -arginine methyl ester ( L -NAME)-induced hypertension. Following UNX, the congenic strain developed significantly more UPV and UAV than the ACI progenitor. The differences were even more pronounced when UNX was combined with an L -NAME-induced rise in systolic blood pressure to about 150 mmHg, i.e., the level of hypertension present in the parental FHH strain. These findings indicate that the Rf-1B region of the FHH rat contains at least one gene affecting the susceptibility to progressive renal failure, especially in the presence of an increase in blood pressure. proteinuria; albuminuria; glomerulosclerosis; renal failure; hypertension; congenic rat; fawn-hooded hypertensive rat