title: Gene therapy for a mouse model of glucose transporter-1 deficiency syndrome.
abstract: OBJECTIVE
  We generated an adeno-associated virus (AAV) vector in which the humanSLC2A1gene was expressed under the synapsin I promoter (AAV-hSLC2A1) and examined if AAV-hSLC2A1administration can lead to functional improvement inGLUT1-deficient mice.
  
  
  METHODS
  AAV-hSLC2A1was injected into heterozygous knock-out murineGlut1(GLUT1+/-) mice intraperitoneally (systemic; 1.85 × 1011vg/mouse) or intra-cerebroventricularly (local; 1.85 × 1010vg/mouse). We analyzed GLUT1 mRNA and protein expression, motor function using rota-rod and footprint tests, and blood and cerebrospinal fluid (CSF) glucose levels.
  
  
  RESULTS
  Vector-derived RNA was detected in the cerebrum for both injection routes. In the intra-cerebroventricular injection group, exogenous GLUT1 protein was strongly expressed in the cerebral cortex and hippocampus near the injection site. In the intraperitoneal injection group, exogenous GLUT1 protein was mildly expressed in neural cells throughout the entire central nervous system. The motor function test and CSF/blood glucose ratio were significantly improved following intra-cerebroventricular injection.
  
  
  CONCLUSIONS
  AAV-hSLC2A1administration produced exogenous GLUT1 in neural cells and improved CSF glucose levels and motor function of heterozygous knock-out murine Glut1 mice.
authors.affiliation: Department of Pediatrics, Jichi Medical University, Tochigi, Japan.
authors.forename: Sachie
authors.initials: S
authors.lastname: Nakamura
authors.affiliation: Department of Pediatrics, Jichi Medical University, Tochigi, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Osaka
authors.affiliation: Division of Neurology, Jichi Medical University, Tochigi, Japan; Center for Gene and Cell Therapy, The Institute of Medical Science, The University of Tokyo, Japan.
authors.forename: Shin-Ichi
authors.initials: SI
authors.lastname: Muramatsu
authors.affiliation: Division of Neurology, Jichi Medical University, Tochigi, Japan.
authors.forename: Naomi
authors.initials: N
authors.lastname: Takino
authors.affiliation: Division of Neurology, Jichi Medical University, Tochigi, Japan.
authors.forename: Mika
authors.initials: M
authors.lastname: Ito
authors.affiliation: Department of Pediatrics, Jichi Medical University, Tochigi, Japan.
authors.forename: Shiho
authors.initials: S
authors.lastname: Aoki
authors.affiliation: Department of Pediatrics, Jichi Medical University, Tochigi, Japan.
authors.forename: Eriko F
authors.initials: EF
authors.lastname: Jimbo
authors.affiliation: Department of Neurosurgery, Jichi Medical University, Tochigi, Japan.
authors.forename: Kuniko
authors.initials: K
authors.lastname: Shimazaki
authors.affiliation: Division of Brain and Neurophysiology, Department of Physiology, Jichi Medical University, Tochigi, Japan.
authors.forename: Tatsushi
authors.initials: T
authors.lastname: Onaka
authors.affiliation: Department of Pharmaceutical Microbiology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Sumio
authors.initials: S
authors.lastname: Ohtsuki
authors.affiliation: Division of Membrane Transport and Drug Targeting, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Terasaki
authors.affiliation: Department of Pediatrics, Jichi Medical University, Tochigi, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Yamagata
keywords: Adeno-associated virus (AAV); GLUT1; Gene therapy; Glucose transporter I deficiency syndrome (GLUT1DS); SLC2A1