Abstract
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.
Original language | English (US) |
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Pages (from-to) | 1169-1179 |
Number of pages | 11 |
Journal | Human molecular genetics |
Volume | 15 |
Issue number | 7 |
DOIs | |
State | Published - Apr 1 2006 |
ASJC Scopus subject areas
- Molecular Biology
- Genetics
- Genetics(clinical)