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, Darryl C. De Vivo
2006 Human Molecular Genetics  
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 1/2 mice have epileptiform discharges
more » ... 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 1/2 murine phenotype mimics the classical human presentation of Glut-1 DS. This GLUT-1 1/2 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.
doi:10.1093/hmg/ddl032 pmid:16497725 fatcat:xfawj3h62ffu7gxktevxt6whfi