Transgenic Mice Over-expressing Dicarbonyl/L-xylulose Reductase Gene Crossed with KK-Ay Diabetic Model Mice: An Animal Model for the Metabolism of Renal Carbonyl Compounds

Abstract

Carbonyl compounds in the blood stream tend to accumulate in the kidney

Suppression of AGE Precursor Formation Following Unilateral Ureteral Obstruction in Mouse Kidneys by Transgenic Expression of α-Dicarbonyl/L-Xylulose Reductase

“…13,14) To examine the relevance of DCXR in the kidney, we generated transgenic (Tg) mice for DCXR. 15) Further crossing the DCXR Tg mice with KK-A y type 2 diabetic model mice, we found that over-expression of DCXR suppressed the increase in body weight and serum glucose levels associated with a diabetes-prone genetic background in the hybrid Tg/A y mice as compared to their +/A y littermates. 15) In this study, we investigated the relevance of DCXR in the clearance of oxidative stress and subsequent fibrosis by employing an acute renal failure model, UUO, which is known to generate oxidative stress in obstructed kidneys.…”

“…15) Further crossing the DCXR Tg mice with KK-A y type 2 diabetic model mice, we found that over-expression of DCXR suppressed the increase in body weight and serum glucose levels associated with a diabetes-prone genetic background in the hybrid Tg/A y mice as compared to their +/A y littermates. 15) In this study, we investigated the relevance of DCXR in the clearance of oxidative stress and subsequent fibrosis by employing an acute renal failure model, UUO, which is known to generate oxidative stress in obstructed kidneys. 16,17) The accumulation of renal dicarbonyls in the UUO-operated DCXR Tg mice was measured by ESI/LC/MS, and the expression of a collagen type III gene was monitored by in situ hybridization together with an immunohistochemical examination of the DCXR protein.…”

“…Wistar male rats (7 weeks old), and male mice (12-14 weeks old) transgenic for DCXR protein (line #4001) previously generated by introducing mouse dcxr cDNA into FVB mice 15) were used. The animals were housed in an approved animal care facility at Taisho Pharmaceutical Co., Ltd., and had free access to food and water.…”

“…15,18) These mice overexpressed DCXR throughout the body. Within the renal tubules, expression was most prominent at the collecting tubules and ducts together with moderate expression in other parts of the tubules.…”

“…Under normal conditions, homozygous and heterozygous mice expressed 6-fold and 3-fold DCXR protein respectively as compared to the wild type as measured by quantifying western blots of the kidney extracts. 15) We examined the abundance of transgenic DCXR protein following UUO treatment in the kidneys of these mice. As shown in Fig.…”