Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Type Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse Generation +pN1 Generation Definitions   Donating Investigator Dr. Gregg Homanics,   University of Pittsburgh

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.

Control Information

	Control
	Heterozygote from the colony
	Wild-type from the colony
	000664 C57BL/6J	(approximate)
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Glra1

001278	B6C3Fe a/a-Glra1spd/J
004109	C57BL/6J-Glra1nmf11/J
000536	C57BL/6J-Glra1spd-ot/J
017522	STOCK Glra1tm2.1Geh/J

View Strains carrying other alleles of Glra1     (4 strains)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI

- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested. Hyperekplexia, Hereditary 1; HKPX1   (GLRA1)

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Glra1^tm1.1Geh/Glra1^tm1.1Geh

        involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * C57BL/6J * SJL

• behavior/neurological phenotype
• altered righting response
  • after injection with ketamine and flurazepam, mice exhibit increased duration of loss of righting reflex compared with similarly treated wild-type mice   (MGI Ref ID J:177105)
• impaired coordination   (MGI Ref ID J:177105)
• increased startle reflex   (MGI Ref ID J:177105)
• increased susceptibility to pharmacologically induced seizures
  • induced by strychnine and pentylenetetrazole   (MGI Ref ID J:177105)
• tremors
  • muscle tremors   (MGI Ref ID J:177105)
• growth/size phenotype
• decreased body weight   (MGI Ref ID J:177105)
• nervous system phenotype
• increased susceptibility to pharmacologically induced seizures
  • induced by strychnine and pentylenetetrazole   (MGI Ref ID J:177105)

View Research Applications

Research Applications

This mouse can be used to support research in many areas including:

Cell Biology Research
Channel and Transporter Defects
      chloride: glycine receptor

Neurobiology Research
Channel and Transporter Defects
      chloride: glycine receptor
Neurotransmitter Receptor and Synaptic Vesicle Defects
Receptor Defects
      glycine

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Glra1tm1.1Geh
Allele Name		targeted mutation 1.1, Gregg E Homanics
Allele Type		Targeted (knock-in)
Common Name(s)		alpha1(Q266I);
Mutation Made By		Dr. Gregg Homanics,   University of Pittsburgh
Strain of Origin		(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
Promoter		Glra1, glycine receptor, alpha 1 subunit, mouse, laboratory
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. [MGI Ref ID J:177105]

Genotyping

Genotyping Information

Genotyping Protocols

Glra1^tm1.1Geh, Pyrosequencing

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Homanics GE. 2011. Direct Data Submission 2011/10/27 MGI Direct Data Submission :.  [MGI Ref ID J:177105]

Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.

Colony Maintenance

Breeding & Husbandry	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.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

Control Information

	Control
	Heterozygote from the colony
	Wild-type from the colony
	000664 C57BL/6J	(approximate)
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

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The Jackson Laboratory's Genotype Promise

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.

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