A mouse model for Glut-1 haploinsufficiency
A mouse model for Glut-1 haploinsufficiency
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DOI：
10.1093/hmg/ddl032
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发表时间：
2006-04-01
影响因子：
3.5
通讯作者：
De Vivo, DC
中科院分区：
文献类型：
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作者：
Wang, D;Pascual, JM;De Vivo, DC
Glut-1缺乏综合征（Glut-1 DS，OMIM #606777）的特征在于婴儿癫痫发作、发育迟缓、获得性小头畸形和低糖血症。它是由血脑屏障己糖载体的单倍不足引起的。GLUT-1基因的杂合突变或半合子导致Glut-1 DS。我们通过靶向破坏小鼠GLUT-1基因的启动子和外显子1区域来产生杂合单倍不足小鼠模型。GLUT-1（+/-）小鼠在脑电图（EEG）上具有癫痫样放电、运动活动受损、不协调、低血糖、脑小畸形、通过正电子发射断层扫描（PET）扫描测量的脑葡萄糖摄取减少和通过蛋白质印迹测量的脑Glut-1表达减少（66%）。GLUT-1（+/-）鼠表型模拟Glut-1 DS的经典人类呈递。该GLUT-1（+/-）小鼠模型为研究Glut-1功能、检查体内Glut-1 DS的病理生理学和评价新的治疗策略创造了机会。
Glut-1 deficiency syndrome (Glut-1 DS, OMIM #606777) is characterized by infantile seizures, developmental delay, acquired microcephaly and hypoglycorrhachia. It is caused by haploinsufficiency of the blood-brain barrier hexose carrier. Heterozygous mutations or hemizygosity of the GLUT-1 gene cause Glut-1 DS. We generated a heterozygous haploinsufficient mouse model by targeted disruption of the promoter and exon 1 regions of the mouse GLUT-1 gene. GLUT-1(+/-) mice have epileptiform discharges on electroencephalography (EEG), impaired motor activity, incoordination, hypoglycorrhachia, microencephaly, decreased brain glucose uptake as measured by positron emission tomography (PET) scan and decreased brain Glut-1 expression by western blot (66%). The GLUT-1(+/-) murine phenotype mimics the classical human presentation of Glut-1 DS. This GLUT-1(+/-) mouse model creates an opportunity to investigate Glut-1 function, to examine the pathophysiology of Glut-1 DS in vivo and to evaluate new treatment strategies.