Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Mating System Homozygote x Homozygote         (Female x Male)   01-APR-13 Species laboratory mouse Generation N10pN1+F1 (11-MAR-13) Generation Definitions   Donating Investigator Beth Levine,   University of Texas Southwestern Medical

Description
B cell leukemia/lymphoma 2 (BCL2) is an anti-apoptotic, anti-autophagy protein that inhibits autophagy by interacting with Beclin 1 (BECN1). Disruption of the BCL2-BECN1 complex is necessary for stimulus (exercise or starvation)- induced autophagy. Bcl2^AAA mice carry alanine substitutions in three conserved phosphorylation sites (T69A, S70A, S84A) that prevent stimulus-induced disruption of the BCL2-BECN1 complex and autophagy activation. Homozygous mice are viable and fertile. During acute exercise, mice exhibit decreased endurance, impaired insulin sensitivity, altered glucose metabolism and impaired protection against glucose intolerance from high fat diet. Bcl2^AAA mice may be useful in studies of induced autophagy, metabolism, and exercise.

Development
A targeting vector containing an frt-flanked puromycin resistance cassette was used to insert alanine substitutions into amino acid residues 69 (threonine), 70 (serine), and 84 (serine) of the Bcl2 gene (Bcl2^AAA). The alanine substitutions were directed to three conserved phosphorylation sites of the exon 2 loop region. The construct was electroporated into 129X1/SvJ-derived RW4 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts and resulting chimeric mice were bred with B6;SJL-Tg(ACTFLPe)9205Dym/J to remove the puro cassette. Mice were backcrossed to C57BL/6J for more than 10 generations.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Bcl2

003082	129S1/SvImJ-Bcl2tm1Mpin/J
003069	B6.NOD-(D1Mit3-Bcl2) (D17Mit21-D17Mit10)/LtJ
003062	B6.NOD-(D1Mit3-Bcl2)/J
002265	B6;129S2-Bcl2tm1Sjk/J
008882	STOCK Bcl2tm1Irt/J

View Strains carrying other alleles of Bcl2     (5 strains)

Additional Web Information

Use of MICE by companies or for-profit entities requires a license prior to shipping.

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. B-Cell Cll/Lymphoma 2; BCL2   (BCL2)

View Research Applications

Research Applications

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

Diabetes and Obesity Research
Insulin Resistance

Metabolism Research

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Bcl2tm1.1Sjk
Allele Name		targeted mutation 1.1, Stanley Korsmeyer
Allele Type		Targeted (knock-in)
Common Name(s)		Bcl2AAA; Bcl2tm1.1Blev;
Mutation Made By		Beth Levine,   University of Texas Southwestern Medical
Strain of Origin		129X1/SvJ
Promoter		Bcl2, B cell leukemia/lymphoma 2, mouse, laboratory
Molecular Note		Nucleotide substitutions in exon 2 were used to replace the threonine at 69 and serines at positions 70 and 84 with alanines (T69A, S70A and S84A). Flp-mediated recombination removes the puro cassette inserted downstream of the modified exon 2. [MGI Ref ID J:181308]

Genotyping

Genotyping Information

Genotyping Protocols

Bcl2^tm1.1SjkPyro, Pyrosequencing

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

He C; Bassik MC; Moresi V; Sun K; Wei Y; Zou Z; An Z; Loh J; Fisher J; Sun Q; Korsmeyer S; Packer M; May HI; Hill JA; Virgin HW; Gilpin C; Xiao G; Bassel-Duby R; Scherer PE; Levine B. 2012. Exercise-induced BCL2-regulated autophagy is required for muscle glucose homeostasis. Nature 481(7382):511-5. [PubMed: 22258505]  [MGI Ref ID J:181308]

Additional References

Bcl2^tm1.1Sjk related

He C; Sumpter R Jr; Levine B. 2012. Exercise induces autophagy in peripheral tissues and in the brain. Autophagy 8(10):1548-51. [PubMed: 22892563]  [MGI Ref ID J:192952]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           FGB29

Colony Maintenance

Breeding & Husbandry	While maintaining a live colony, these mice are bred as homozygotes.
Mating System	Homozygote x Homozygote         (Female x Male)   01-APR-13

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

Payment Terms and Conditions

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.

See Terms of Use tab for General Terms and Conditions

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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