Overview

Also Known As:alpha2i TG

α 2i TG mice express the inactive D157A mutant form of the rat Prkaa2 under the direction of the muscle creatine kinase promoter. Loss of AMPK α 2 activity results in inhibition of glucose transport in AICAR- and rotenon-stimulated muscle. This strain may be useful for studying mechanisms of glucose transport regulation.

Donating Investigator

Laurie J. Goodyear, Brigham and Women’s Hospital and Harvard Medical School

Michael Hirshman, Joslin Diabetes Center

Genetic overview

Genetic Background	Generation

Tg(Ckm-Prkaa2*D157A)1Ljg

Allele Type
Transgenic (Inserted expressed sequence)

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Research Applications

Diabetes and Obesity Research
Metabolism Research

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Details

Detailed Description

α 2i TG mice express the D157A mutant form of the rat Prkaa2 (protein kinase, AMP-activated, alpha 2 catalytic subunit) cDNA under the direction of the muscle creatine kinase promoter. PRKAA2 is the catalytic subunit of the AMP-activated protein kinase an energy-sensing enzyme that responds to metabolic stress. The D157A amino acid substitution renders the catalytic subunit inactive resulting in almost undetectable AMPKα 2 basal activity, and reduced AMPKα 1 activity. Hemizygous and homozygous mice are viable and fertile. Known AMPK stimuli AICAR and rotenone, but not muscle contraction or sorbitol, inhibit in vitro glucose transport in extensor digitorum longus muscles. In vivo, contraction-stimulated glucose transport is normal. This strain may be useful for studying mechanisms of glucose transport regulation.

Development

The transgenic construct contains a rat cDNA containing the Prkaa2 gene modified by site-directed mutagenesis to include the D157A mutation under the control of the muscle creatine kinase promoter. The mutation changes the aspartic acid at residue 157 to alanine thus inactivating the catalytic alpha 2 subunit. The inactive alpha 2 subunit is tagged with a hemaglutinin epitope at the amino terminus. The transgene was injected into the pronuclei of FVB/N mouse oocytes. Mice from founder line 1 bred with FVB/N mice to establish the colony. Upon arrival, mice were bred to FVB/NJ for at least 1 generation to establish the colony.

Expression Data

Expressed Gene	Prkaa2, protein kinase AMP-activated catalytic subunit alpha 2, rat
Site of Expression

Control Suggestions

001800 FVB/NJ

Additional Information

Considerations for Choosing Controls

Selected References

Fujii N; Hirshman MF; Kane EM; Ho RC; Peter LE; Seifert MM; Goodyear LJ. 2005. AMP-activated protein kinase alpha2 activity is not essential for contraction- and hyperosmolarity-induced glucose transport in skeletal muscle. J Biol Chem 280(47):39033-41PubMed: 16186119 MGI: J:104111

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Genetics

Tg(Ckm-Prkaa2*D157A)1Ljg

Allele Symbol: Tg(Ckm-Prkaa2*D157A)1Ljg

Allele Name	transgene insertion 1, Laurie J Goodyear
Allele Type	Transgenic (Inserted expressed sequence)
Allele Synonym(s)	alpha2i TG; AMPKalpha2i TG
Gene Symbol and Name	Tg(Ckm-Prkaa2*D157A)1Ljg, transgene insertion 1, Laurie J Goodyear
Gene Synonym(s)
Promoter	Ckm, creatine kinase, muscle, mouse, laboratory
Expressed Gene	Prkaa2, protein kinase AMP-activated catalytic subunit alpha 2, rat
Strain of Origin	FVB/N
Chromosome	UN
Molecular Note	The transgenic construct contains a rat cDNA containing the Prkaa2 gene modified by site-directed mutagenesis to contain the D157A mutation under the control of the muscle creatine kinase promoter. The mutation changes the aspartic acid at residue 157 to alanine thus inactivating the catalytic alpha 2 subunit. The inactive alpha 2 subunit is tagged with a hemaglutinin epitope at the amino terminus. Expression of endogenous Prkaa2 is detectable only after very long exposure times and transgene expression occurs in skeletal muscle.

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Diabetes and Obesity Research
Metabolism Research

Mammalian Phenotype Terms by Genotype

References

Fujii N; Hirshman MF; Kane EM; Ho RC; Peter LE; Seifert MM; Goodyear LJ. 2005. AMP-activated protein kinase alpha2 activity is not essential for contraction- and hyperosmolarity-induced glucose transport in skeletal muscle. J Biol Chem 280(47):39033-41PubMed: 16186119 MGI: J:104111

Additional - Tg(Ckm-Prkaa2*D157A)1Ljg related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Tg(Ckm-Prkaa2*D157A)1Ljg
- Genotyping resources and troubleshooting
Breeding Considerations

While maintaining a live colony, these mice can be bred as homozygotes.
- Additional Breeding and Husbandry Support
Citation
When using the alpha2i TG mouse strain in a publication, please cite the originating article(s) and include MMRRC stock #41177 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

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

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. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

Terms Of Use

General Terms and Conditions

See MMRRC for Additional Conditions of Distribution

Questions about Terms of Use

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Also Known As:alpha2i TG

Donating Investigator

Genetic overview

Research Applications

Detailed Description

Development

Expression Data

Control Suggestions

Additional Information

Selected References

Tg(Ckm-Prkaa2*D157A)1Ljg

Allele Symbol: Tg(Ckm-Prkaa2*D157A)1Ljg

Disease Terms

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

References

Additional - Tg(Ckm-Prkaa2*D157A)1Ljg related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

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

The Jackson Laboratory's Genotype Promise

Terms Of Use

Licensing Information