A mouse model for Glut-1 haploinsufficiency.
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.
Wang
Dong
D
Colleen Giblin Laboratories for Pediatric Neurology Research, Department of Neurology, Columbia University, New York, NY 10032, USA.
Pascual
Juan M
JM
Yang
Hong
H
Engelstad
Kristin
K
Mao
Xia
X
Cheng
Jianfeng
J
Yoo
Jong
J
Noebels
Jeffrey L
JL
De Vivo
Darryl C
DC
D000818:Animals; D001921:Brain / Q000378:metabolism; D004569:Electroencephalography; D004622:Embryo, Mammalian / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000378:metabolism; D051272:Glucose Transporter Type 1 / Q000235:genetics* / Q000378:metabolism; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D051379:Mice; D023421:Models, Animal; D008957:Models, Genetic; D009043:Motor Activity / Q000235:genetics / Q000502:physiology; D010641:Phenotype; D012640:Seizures / Q000378:metabolism
D051272:Glucose Transporter Type 1; D005947:Glucose