Rf‐1 Implicated in the Nephropathy of the T2DN Rat

Abstract

The present study implicates the Rf-1 locus, independent of diabetes, in the development of nephropathy in type II diabetic nephropathy (T2DN) rats. T2DN and Fawn-Hooded Hypertensive (FHH) rats appear to require preexisting diabetes or hypertension, respectively, to develop renal disease. However, data from a cross between T2DN and FHH indicated that the F1 progeny developed proteinuria without the predisposing conditions. These results suggested that Rf-1 plays a role in the development of renal disease in the T2DN rat, independent of diabetes, but can not exclude the effects of other Rf loci (Rf-2, 3, 4 or 5). To test the role of Rf-1 in the development of nephropathy in the T2DN rat, two additional studies were conducted. 1) A reciprocal cross between T2DN and FHH. BN1Rf−1, a congenic containing a Brown Norway (BN) insert covering Rf-1 on an FHH background. The F1 progeny are not diabetic as assessed by intraperitoneal glucose tolerance test (IPGTT) and do not develop renal disease as assessed by urinary albumin (UAV). This result rules out an FHH background effect. 2) A reciprocal cross between T2DN and FHH. BN1Rf−2, a second congenic containing a BN insert that covers only the Rf-2 locus. The F1 animals are non-diabetic, but develop progressive renal disease, which is clinically relevant by 52 weeks of age (UAV=52.64±9.09 mg/day), thus implicating Rf-1 alleles Funding: MCW Internal