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.
Gregg E Homanics, University of Pittsburgh
Genetic Background | Generation |
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Allele Type | Gene Symbol | Gene Name |
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Targeted (Not Specified) | Glra1 | glycine receptor, alpha 1 subunit |
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.
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 Name | targeted mutation 1.1, Gregg E Homanics |
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Allele Type | Targeted (Not Specified) |
Allele Synonym(s) | alpha1(Q266I) |
Gene Symbol and Name | Glra1, glycine receptor, alpha 1 subunit |
Gene Synonym(s) | |
Promoter | Glra1, glycine receptor, alpha 1 subunit, mouse, laboratory |
Strain of Origin | (129X1/SvJ x 129S1/Sv)F1-Kitl+ |
Chromosome | 11 |
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. A point mutation was introduced in exon 7, resulting in the amino acid mutation Q266I. Flp-mediated recombination removed the neo cassette. |
Mutations Made By | Gregg Homanics, University of Pittsburgh |
When maintaining a live colony, heterozygous mice may be bred to wildtype mice from the colony or to C57BL/6J inbred mice (Stock No. 000664). The donating investigator reports that these mice die or are sacrificed by 2-3 weeks of age.
When using the STOCK Glra1tm1.1Geh/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #017521 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Heterozygous or wildtype for Glra1<tm1.1Geh> |
Frozen Mouse Embryo | STOCK Glra1<tm1.1Geh>/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | STOCK Glra1<tm1.1Geh>/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | STOCK Glra1<tm1.1Geh>/J Frozen Embryo | $3373.50 |
Frozen Mouse Embryo | STOCK Glra1<tm1.1Geh>/J Frozen Embryo | $3373.50 |
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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.
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