X-linked glycerol kinase deficiency in the mouse leads to growth retardation, altered fat metabolism, autonomous glucocorticoid secretion and neonatal death
X-linked glycerol kinase deficiency in the mouse leads to growth retardation, altered fat metabolism, autonomous glucocorticoid secretion and neonatal death
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DOI：
10.1093/hmg/6.11.1803
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发表时间：
1997-10-01
影响因子：
3.5
通讯作者：
Craigen, WJ
中科院分区：
文献类型：
--
作者：
Huq, AHMM;Lovell, RS;Craigen, WJ
甘油激酶是一种X染色体编码的酶，参与内源性和膳食甘油脂的代谢，其在哺乳动物中活性的生理意义尚不清楚，人类的甘油激酶缺乏症是一种孤立的酶缺乏症，或者是与杜氏肌营养不良和先天性肾上腺发育不全相关的连续基因缺失综合征的一部分，孤立的甘油激酶缺乏症具有不稳定的表型。虽然最近有基因内突变的报道，但其表型变异的病理生理基础尚不清楚。为了更好地了解甘油激酶的生理意义及其缺乏的病理生理，我们通过基因靶向培养了甘油激酶缺陷小鼠，突变的雄性小鼠在出生时表现正常。但表现出出生后生长迟缓，脂肪代谢改变，伴严重高甘油血症和游离脂肪酸升高，糖皮质激素自主合成，3-4日龄死亡。杂合雌性健康，生化正常。
Glycerol kinase is an X chromosome-encoded enzyme involved in the metabolism of endogenous and dietary glycerolipids, The physiological significance of its activity in mammals is not well understood, Glycerol kinase deficiency in humans occurs as an isolated enzyme deficiency or as part of a contiguous gene deletion syndrome in variable association with Duchenne muscular dystrophy and adrenal hypoplasia congenita, Isolated glycerol kinase deficiency has an inconstant phenotype, ranging from asymptomatic hyperglycerolemia to a severe metabolic disorder with growth and psychomotor retardation, Although intragenic mutations were reported recently, the pathophysiological basis for the phenotypic variability remains unknown, To understand better the physiological significance of glycerol kinase and the pathophysiology of its deficiency, we generated glycerol kinase-deficient mice by gene targeting, Mutant male mice appear normal at birth, but exhibit postnatal growth retardation, altered fat metabolism with profound hyperglycerolemia and elevated free fatty acids, autonomous glucocorticoid synthesis and death by 3-4 days of age, Heterozygous females are healthy and biochemically normal, The biochemical features observed in glycerol kinase-deficient mice provide the basis for further investigations into the pathogenesis of the human disorder.