A mouse model of galactose-induced cataracts.
Galactokinase (GK; EC 2.7.1.6) is the first enzyme in the metabolism of galactose. In humans, GK deficiency results in congenital cataracts due to an accumulation of galactitol within the lens. In an attempt to make a galactosemic animal model, we cloned the mouse GK gene (Glk1) and disrupted it by gene targeting. As expected, galactose was very poorly metabolized in GK-deficient mice. In addition, both galactose and galactitol accumulated in tissues of GK-deficient mice. Surprisingly, the GK-deficient animals did not form cataracts even when fed a high galactose diet. However, the introduction of a human aldose reductase transgene into a GK-deficient background resulted in cataract formation within the first postnatal day. This mouse represents the first mouse model for congenital galactosemic cataract.
Department of Ophthalmology and Genetics, University of Pennsylvania, Room 313 Stellar Chance, 422 Curie Boulevard, Philadelphia, PA 19104, USA.
Y
Y
Ai
Z
Z
Zheng
A
A
O'Brien-Jenkins
D J
DJ
Bernard
T
T
Wynshaw-Boris
C
C
Ning
R
R
Reynolds
S
S
Segal
K
K
Huang
D
D
Stambolian
D000449:Aldehyde Reductase / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D002386:Cataract / Q000201:enzymology* / Q000235:genetics; D018076:DNA, Complementary; D004195:Disease Models, Animal; D004376:Galactitol / Q000378:metabolism; D005686:Galactokinase / Q000235:genetics / Q000502:physiology*; D005690:Galactose / Q000378:metabolism*; D015870:Gene Expression; D018390:Gene Targeting; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction
D018076:DNA, Complementary; D004376:Galactitol; D000449:Aldehyde Reductase; D005686:Galactokinase; D005690:Galactose