A mouse model of galactose-induced cataracts
A mouse model of galactose-induced cataracts
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DOI：
10.1093/hmg/9.12.1821
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发表时间：
2000-07-22
影响因子：
3.5
通讯作者：
Stambolian, D
中科院分区：
文献类型：
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作者：
Ai, YJ;Zheng, Z;Stambolian, D
半乳糖激酶（GK；EC 2.7.1.6）是半乳糖代谢中的第一种酶。在人类中，GK 缺乏会因半乳糖醇在晶状体内积聚而导致先天性白内障。为了建立半乳糖动物模型，我们克隆了小鼠 GK 基因 (Glk1)，并通过基因打靶破坏了它。正如预期的那样，GK 缺陷小鼠体内的半乳糖代谢非常差。此外，半乳糖和半乳糖醇均在 GK 缺陷小鼠的组织中积累。令人惊讶的是，即使喂食高半乳糖饮食，GK 缺乏的动物也没有形成白内障。然而，将人醛糖还原酶转基因引入 GK 缺陷背景会导致出生后第一天内形成白内障。该小鼠代表了第一个先天性半乳糖性白内障小鼠模型。
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.