STOCK Glra1^tm1.1Geh/J

Stock number: 017521
Research areas: Cell Biology Research, Neurobiology Research

Description

These α1(Q266I) mice contain the amino acid mutation Q266I in exon 7 of the glycine receptor, alpha 1 subunit (Glra1) gene. These mice may be useful for studying glycine receptor sensitivity to alcohols and volatile anesthetics.

Detailed description

These α1(Q266I) mice contain the amino acid mutation Q266I in exon 7 of the glycine receptor, alpha 1 subunit (Glra1) gene. Heterozygotes are viable and fertile. Homozygotes die at about 2-3 weeks of age (or should be sacrificed for humane reasons). Glycine receptors are ligand-gated chloride channels found in the brain stem, spinal cord, hippocampus, cerebellum, nucleus accumbens, and olfactory bulb where they mediate inhibitory neurotransmissions. Their inhibitory function is enhanced by alcohols and volatile anesthetics. In humans, disruption of the receptor has been linked to Hyperekplexia (aka Stiff person syndrome), neonatal apnea, excessive movement during sleep, brain damage, epilepsy, a head-retraction reflex and cases of Sudden Infant Death. This strain contains a Q266I mutation in the in transmembrane domain 2, which reduces glycine receptor sensitivity and eliminates ethanol potentiation of the receptor. These mice exhibit increased startle response, increased sensitivity to strychnine and pentylenetetrazole induced seizures, muscle tremors, motor control abnormalities, and reduced body weight. They also display severely decreased receptor response to isoflurane and chloroform. They show increased duration of the loss of righting reflex after injection with ketamine, and flurazepam. These mice may be useful for studying glycine receptor sensitivity to alcohols and volatile anesthetics.

Development

A targeting construct was designed to insert a frt-flanked neomycin (neo) resistance cassette in opposite orientation to the gene, downstream of exon 7 of the glycine receptor, alpha 1 subunit (Glra1) gene. A point mutation was introduced in exon 7, resulting in the amino acid mutation Q266I. This targeting construct was electroporated into (129X1/SvJ x 129S1/Sv)F1-Kitl⁺-derived R1 embryonic stem (ES) cells and correctly targeted ES cells were injected into C57BL/6J blastocysts. Chimeric males were bred to female C57BL/6J mice and the resulting offspring were subsequently bred to mice carrying Tg(ACTFLPe)9205Dym on a B6 background to remove the neo cassette. These α1(Q266I) mice were then maintained on a mixed background. Upon arrival at The Jackson Laboratory, these were bred to C57BL/6J (Stock No. 000664) mice for at least one generation.

Allele

Symbol: Glra1^tm1.1Geh
Name: targeted mutation 1.1, Gregg E Homanics
MGI accession ID: MGI:5293666
Generation method: Targeted
Attributes: Not Specified
Marker symbol: Glra1
Marker name: glycine receptor, alpha 1 subunit
Chromosome: 11
Strain of origin: (129X1/SvJ x 129S1/Sv)F1-Kitl⁺
Molecular note: A targeting construct was designed to insert a frt-flanked neomycin (neo) resistance cassette in opposite orientation to the gene, downstream of exon 7 of the glycine receptor, alpha 1 subunit (Glra1) gene. Nucleotide substitutions (CAG to ATC) introduced in exon 7 resulted in the amino acid mutation Q266I. Flp-mediated recombination removed the neo cassette.