Assignment of the gene encoding renin binding protein (Renbp) to rat chromosome Xq37 by in situ hybridization and radiation hybrid mapping

Abstract

The renin-angiotensin system (RAS) plays a crucial role in the regulation of blood pressure (Laragh, 1995). Within the RAS, the physiological relevance of renin binding protein (RnBP) has been controversial for several years (Schmitz et al., 2000). Originally, RnBP was identified as a protein in the kidney that was capable of binding renin in renal homogenates giving rise to a complex designated high molecular weight renin (Takahashi et al., 1983). It was subsequently proposed that RnBP might act as an endogenous cellular renin inhibitor. Recent studies demonstrated that human RnBP is the enzyme N-acetyl-D-glucosamine (GlcNAc) 2-epimerase (Takahashi et al., 1999). Moreover, gene-targeting experiments in the mouse excluded a specific interaction between RnBP and renin in the kidney or in the circulating RAS of the mouse (Schmitz et al., 2000). So far, the gene encoding RnBP has been mapped on chromosome X in different mammals: Xq28 in human (van den Ouweland et al., 1994), X 29.53 cM in mouse (http:// www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=19703) and X in canine (Stoy et al., 1998). As mapping data for the rat homolog Renbp is still lacking, it is unclear whether this gene is located in blood pressure quantitative trait loci (QTL) termed BP/SP-2 and SS-X on rat chromosome X. BP/SP2 has been identified in an intercross between the stroke prone spontaneously hypertensive rat (SHRSP) and the normotensive Wistar-Kyoto (WKY) rat (Hilbert et al., 1991) and SS-X has been characterized in the Sabra hypertension-prone rat (Yagil et al., 1999). We therefore set out to test the chromosome location of Renbp by performing chromosomal mapping analysis in the rat using fluorescence in situ hybridization (FISH) and radiation hybrid (RH) mapping.