GALACTOSE-INDUCED ALBUMINURIA IN TRANSGENIC MICE EXPRESSING HUMAN ALDOSE REDUCTASE

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 dec reased thereafter in spite of the steady increase of renal galactitol. On the other hand, the increased urine volume (UV) in Gal-fed mice, t he suppression of UV and UAE in Gal-fed hAR-Tg with aldose reductase i nhibitor (ARI) were observed. The similar time course between the chan ges of UV and UAE, and the positive correlation between UV and UAE sug gest that galactitol accumulation via the polyol pathway is partially responsible for the increased UV and increased UAE in Gal-fed mice.