Age-related pathophysiological changes in rat oligomeganephronic hypoplastic kidney

Abstract

Rat male hypogonadism (hgn/hgn) is accompanied by oligomeganephronic hypoplastic kidney (HPK), in which each kidney contains one quarter the number of nephrons present in a normal kidney. The nephrons of the HPK are extremely hypertrophied. These characters were apparently common to human oligomeganephronia (OMN). To determine the age-related changes in renal pathophysiology in HPK rats, we measured several parameters of renal function at 70 days, 140 days, 210 days, and 280 days of age. At all time points, relative kidney weight was significantly smaller in HPK rats than in their normal litter mates. In HPK rats, both polyuria and polydipsia became more severe with advancing age. Although creatinine clearance (Ccr) and urinary nitrogen clearance (Cun) were significantly lower in HPK than in normal rats, the values did not decrease with age. A severe form of glomerulosclerosis, as well as interstitial infiltration and cystic dilation of tubules with proteinaceous luminal casts, was observed in the inner cortex and medulla of HPK rats at advanced age. In these animals the surface glomeruli retained their functional architecture but were hypertrophied. Both mean blood pressure (MBP) and proteinuria became more elevated with age in HPK rats, and their urine samples included considerable amounts of high molecular weight protein. These results suggest that the HPK rat is a suitable model of human OMN.

Reduced Mitotic Activity and Increased Apoptosis of Fetal Sertoli Cells in Rat Hypogonadic (hgn/hgn) Testes

“…The slides were incubated with 3,3'-diaminobenzidine tetrahydrochloride (DAB), counterstained with hematoxylin and examined under a light microscope (BX50; Olympus). Microscopic images were obtained using a Penguin 600CL digital camera system (Pixera Corporation, Osaka, Japan) attached to the microscope [6,7,[17][18][19].…”

“…These animals have one quarter the number of nephrons present in the normal kidney, and their individual nephrons are extremely hypertrophied [6]. Thus, hgn/hgn rats can be used a s a n e x p e r i m e n t a l m o d e l o f h u m a n oligomeganephronia, which progresses to renal insufficiency with advancing age [7].Linkage analysis has shown that the gene responsible for the hgn phenotype is located in an 840-kb region of rat chromosome 10 [8, 9]. The most likely candidate gene in this region is Spag5 (astrin/MAP126) [9].…”

“…These animals have one quarter the number of nephrons present in the normal kidney, and their individual nephrons are extremely hypertrophied [6]. Thus, hgn/hgn rats can be used a s a n e x p e r i m e n t a l m o d e l o f h u m a n oligomeganephronia, which progresses to renal insufficiency with advancing age [7].…”

Duplicated insertion mutation in the microtubule-associated protein Spag5 (astrin/MAP126) and defective proliferation of immature Sertoli cells in rat hypogonadic (hgn/hgn) testes

“…We have described the pathophysiological characters of these hgn/hgn rats, in which testicular dysplasia was used to study testes development , 1993, 2004b, Yagi et al 2006). In addition, we have used the renal hypoplasia occurring in these rats as a model of oligomeganephronia and chronic renal failure (Suzuki & Suzuki, 1995Suzuki et al 1991Suzuki et al , 2005Suzuki et al , 2006. Since no other knockout mouse or mutant rat showing a similar phenotype has been reported, we started linkage analysis in 1997 and located the responsible gene on rat chromosome 10 (Suzuki et al 1999).…”

Age-Related Pathophysiological Changes in Rats with Unilateral Renal Agenesis

“…All male rats were categorized by palpation of the kidneys at 21 days of age, and the diagnosis was confirmed by necropsy [2]. The experimental procedures and care of animals were in accordance with the guidelines of the Animal Care and Use Committee of Nippon Veterinary and Life Science University [29,30].Measurements of food intake, water intake, and urinary volume: Male rats were kept individually in stainless steel metabolic cages (TOYO-RIKO Co., Ltd., Tokyo, Japan). Twenty-four hours food and water intake and 24 hr urinary…”