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.
Laurie J. Goodyear, Brigham and Women’s Hospital and Harvard Medical School
Michael Hirshman, Joslin Diabetes Center
Genetic Background | Generation |
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Allele Type |
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Transgenic (Inserted expressed sequence) |
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.
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.
Expressed Gene | Prkaa2, protein kinase AMP-activated catalytic subunit alpha 2, rat |
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Site of Expression |
Allele Name | transgene insertion 1, Laurie J Goodyear |
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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. |
While maintaining a live colony, these mice can be bred as homozygotes.
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.
Facility Barrier Level Descriptions
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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