GALACTOSE-INDUCED ALBUMINURIA IN TRANSGENIC MICE EXPRESSING HUMAN ALDOSE REDUCTASE

Abstract The effects of 30% galactose (Gal)-feeding on Gal-induced albuminuria were examined in transgenic mice (Tg), in which human aldose reductase (hAR) was expressed by an MHC class I promoter (hAR-Tg). Both in hAR-Tg and the littermates, urinary albumin excretion (UAE) increased and reached its peak at 2 to 4 wks after the start of Gal-feeding, and decreased thereafter in spite of the steady increase of renal galactitol. On the other hand, the increased urine volume (UV) in Gal-fed mice, the suppression of UV and UAE in Gal-fed hAR-Tg with aldose reductase inhibitor (ARI) were observed. The similar time course between the changes of UV and UAE, and the positive correlation between UV and UAE suggest that galactitol accumulation via the polyol pathway is partially responsible for the increased UV and increased UAE in Galfed mice.