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

Research output: Contribution to journalArticle

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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 languageEnglish (US)
Pages (from-to)1169-1179
Number of pages11
JournalHuman Molecular Genetics
Volume15
Issue number7
DOIs
StatePublished - Apr 1 2006

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Haploinsufficiency
Genetic Databases
Microcephaly
Hexoses
Brain
Ataxia
Blood-Brain Barrier
Positron-Emission Tomography
Genes
Electroencephalography
Exons
Seizures
Motor Activity
Western Blotting
Phenotype
Glucose
Mutation
Therapeutics

ASJC Scopus subject areas

  • Genetics

Cite this

Wang, D., Pascual, J. M., Yang, H., Engelstad, K., Mao, X., Cheng, J., ... De Vivo, D. C. (2006). A mouse model for Glut-1 haploinsufficiency. Human Molecular Genetics, 15(7), 1169-1179. https://doi.org/10.1093/hmg/ddl032

A mouse model for Glut-1 haploinsufficiency. / Wang, Dong; Pascual, Juan M.; Yang, Hong; Engelstad, Kristin; Mao, Xia; Cheng, Jianfeng; Yoo, Jong; Noebels, Jeffrey L.; De Vivo, Darryl C.

In: Human Molecular Genetics, Vol. 15, No. 7, 01.04.2006, p. 1169-1179.

Research output: Contribution to journalArticle

Wang, D, Pascual, JM, Yang, H, Engelstad, K, Mao, X, Cheng, J, Yoo, J, Noebels, JL & De Vivo, DC 2006, 'A mouse model for Glut-1 haploinsufficiency', Human Molecular Genetics, vol. 15, no. 7, pp. 1169-1179. https://doi.org/10.1093/hmg/ddl032
Wang D, Pascual JM, Yang H, Engelstad K, Mao X, Cheng J et al. A mouse model for Glut-1 haploinsufficiency. Human Molecular Genetics. 2006 Apr 1;15(7):1169-1179. https://doi.org/10.1093/hmg/ddl032
Wang, Dong ; Pascual, Juan M. ; Yang, Hong ; Engelstad, Kristin ; Mao, Xia ; Cheng, Jianfeng ; Yoo, Jong ; Noebels, Jeffrey L. ; De Vivo, Darryl C. / A mouse model for Glut-1 haploinsufficiency. In: Human Molecular Genetics. 2006 ; Vol. 15, No. 7. pp. 1169-1179.
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