Astrocyte-specific GLT1 inducible knockout mice exhibit pathological repetitive behaviors including excessive and injurious levels of self-grooming and tic-like head shakes; treatment with an N-methyl-D-aspartate (NMDA) receptor antagonist memantine ameliorated these pathological repetitive behaviors (Aida et al., 2015). A survey of 31 patients with WAGR (Wilms tumor, Aniridia, Genitourinary malformations and mental Retardation) syndrome caused by de novo 11p14-p12 deletions found that deletion of SLC1A2 occurred in patients with autism more frequently than in those without autism (Xu et al., 2008).
Molecular Function
This gene encodes a member of a family of solute transporter proteins. The membrane-bound protein is the principal transporter that clears the excitatory neurotransmitter glutamate from the extracellular space at synapses in the central nervous system.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Astroglial glutamate transporter deficiency increases synaptic excitability and leads to pathological repetitive behaviors in mice.
Slc1a2 complete knockouts die prematurely, often due to spontaneous seizures and do not reach adulthood, they also demonstrate neuronal degeneration. The conditional KO, specific to astrocytes and activated in adolescent mice, show increased repetitive and stereotypic behavior.
References
Type
Title
Author, Year
Primary
Astroglial glutamate transporter deficiency increases synaptic excitability and leads to pathological repetitive behaviors in mice.
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Conditional deletion of exon 4 of Slc1a2 gene using Glast-creERT2 (or Slc1a3-cre-ERT2)in astrocytes, after tamoxifen mediated activation of cre at P1
Allele Type: Conditional loss-of-function
Strain of Origin: 129P2/OlaHsd
Genetic Background: ES Cell Line: Mutant ES Cell Line: Model Source:
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Conditional deletion of exon 4 of Slc1a2 gene using Glast-creERT2 (or Slc1a3-cre-ERT2) in astrocytes, after tamoxifen administration for 5 days, daily, from P19 (adolescent)
Allele Type: Conditional loss-of-function
Strain of Origin: 129P2/OlaHsd
Genetic Background: ES Cell Line: Mutant ES Cell Line: Model Source:
Model Type:
Pharmaceutical intervention
Model Genotype:
Homozygous
Mutation:
Adolescent-Slc1a2 CKO mice were treated by intraperitoneal administration of kainic acid (30 mg/kg, Sigma) dissolved in saline, when they were 8-weeks-old, to induce seizures in order to measure seizure susceptibility.
Allele Type: Conditional loss-of-function
Strain of Origin: 129P2/OlaHsd
Genetic Background: ES Cell Line: Mutant ES Cell Line: Model Source:
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Conditional deletion of exon 4 of the Slc1a2 gene using Glast-creERT2(or Slc1a3-cre-ERT2) in astrocytes, after treatment with tamoxifen for 5 days, daily, from 12 weeks of age (adult CKO)
Allele Type: Conditional loss-of-function
Strain of Origin: 129P2/OlaHsd
Genetic Background: ES Cell Line: Mutant ES Cell Line: Model Source:
Description: Early activation of the cre gene by tamoxifen, at p1 in the slc1a2 flox/flox mice, leads to almost complete lack of slc1a2 expression in mice tested at 4 weeks
Exp Paradigm: NA
Description: In the repeated stimulation protocol, instead of a decrease in excitatory post synaptic current(epsc) amplitude seen in control littermates, there is no decrease in the amplitude of epsc in adolescent-slc1a2 brain slices, showing increased glutamate release manifested using this protocol
Exp Paradigm: NA
Description: Kainate injected mutant slc1a2 mice show increased seizure sensitivity or decreased threshold of seizure induction compared to littermate controls, determined using a scoring system of 1-7 level of seizures with a higher percentage of mutants expressing a score of 7(death)
Exp Paradigm: NA
