Journal Article

A mouse model for Glut-1 haploinsufficiency

Dong Wang, Juan M. Pascual, Hong Yang, Kristin Engelstad, Xia Mao, Jianfeng Cheng, Jong Yoo, Jeffrey L. Noebels and Darryl C. De Vivo

in Human Molecular Genetics

Volume 15, issue 7, pages 1169-1179
Published in print April 2006 | ISSN: 0964-6906
Published online February 2006 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/ddl032

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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.

Journal Article.  6803 words.  Illustrated.

Subjects: Genetics and Genomics

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