A mouse model of galactose-induced cataracts

Galactokinase (GK; EC 2.7.1.6) is the first enzyme in the metabolism of gal actose, In humans, GK deficiency results in congenital cataracts due to an accumulation of galactitol within the lens. In an attempt to make a galacto semic animal model, we cloned the mouse GK gene (Glk1) and disrupted it by gene targeting. As expected, galactose was very poorly metabolized in GK-de ficient mice. In addition, both galactose and galactitol accumulated in tis sues of GK-deficient mice. Surprisingly, the GK-deficient animals did not f orm cataracts even when fed a high galactose diet. However, the introductio n of a human aldose reductase transgene into a GK-deficient background resu lted in cataract formation within the first postnatal day. This mouse repre sents the first mouse model for congenital galactosemic cataract.