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.
Ai
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Department of Ophthalmology and Genetics, University of Pennsylvania, Room 313 Stellar Chance, 422 Curie Boulevard, Philadelphia, PA 19104, USA.
Zheng
Z
Z
O'Brien-Jenkins
A
A
Bernard
D J
DJ
Wynshaw-Boris
T
T
Ning
C
C
Reynolds
R
R
Segal
S
S
Huang
K
K
Stambolian
D
D
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