Overview

Mice homozygous for this Akt2 (thymoma viral proto-oncogene 2) mutant allele develop insulin resistance, hyperglycemia, impaired glucose tolerance, abnormal glucose uptake in muscle tissue, increased pancreatic beta-cell mass, and diabetes.

Donating Investigator

Morris J. Birnbaum, Un of Pennsylvania Schl of Medicine

Genetic overview

Genetic Background	Generation

Akt2^tm1.1Mbb

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Akt2	thymoma viral proto-oncogene 2

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Research Applications

Research Tools
Diabetes and Obesity Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

Mice homozygous for this Akt2 (thymoma viral proto-oncogene 2) mutant allele are viable and fertile. Homozygotes develop insulin resistance, hyperglycemia, impaired glucose tolerance, abnormal glucose uptake in muscle tissue, increased pancreatic beta-cell mass, and diabetes.

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.

Development

This mutation was created by Dr. Morris Birnbaum (University of Pennsylvania) by flanking exons 4-5 of the targeted gene with loxP sites. The targeting vector was electroporated into 129P2/OlaHsd-derived E14 embryonic stem (ES) cells, and the chimeric males were bred with C57BL/6 females. Mutant mice were then bred to cre transgenic mice to remove exons 4-5 and bred for an unknown number of generations. These mutant mice on a mixed (approximately 80% C57BL/6J) background were then shipped to Dr. Jan Breslow at The Rockefeller University. Dr. Breslow's lab crossed these mice to another mutant strain and further backcrossed to C57BL/6J for approximately 7 generations prior to arrival at The Jackson Laboratory (as Stock No. 006952). The donating investigators report that 102/104 microsatellite markers indicate C57BL/6J background; the only exceptions are D7Mit21 and D7Mit294. The Y chromosome may not have been fixed to the C57BL/6J genetic background. Upon arrival, some Stock No. 006952 mice were bred to C57BL/6J to isolate the Akt2 mutant allele; generating this single mutant congenic strain (Stock No. 006966).

Control Suggestions

Wild-type from the colony
000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Cho H; Mu J; Kim JK; Thorvaldsen JL; Chu Q; Crenshaw EB 3rd; Kaestner KH; Bartolomei MS; Shulman GI; Birnbaum MJ. 2001. Insulin resistance and a diabetes mellitus-like syndrome in mice lacking the protein kinase Akt2 (PKB beta). Science 292(5522):1728-31PubMed: 11387480 MGI: J:71491
Leavens KF; Easton RM; Shulman GI; Previs SF; Birnbaum MJ. 2009. Akt2 is required for hepatic lipid accumulation in models of insulin resistance. Cell Metab 10(5):405-18PubMed: 19883618 MGI: J:155432

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Genetics

Akt2^tm1.1Mbb

Allele Symbol: Akt2^tm1.1Mbb

Allele Name	targeted mutation 1.1, Morris J Birnbaum
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	Akt2-; Akt2 KO; PKBbeta^-
Gene Symbol and Name	Akt2, thymoma viral proto-oncogene 2
Gene Synonym(s)
Strain of Origin	129P2/OlaHsd
Chromosome	7
Molecular Note	This allele is a derivative of Akt2^tm1Mbb. Cre-mediated recombination in vivo under the control of a 6 kb 5'-flanking sequence from the Pou3f4 gene excised the floxed exons 4 and 5 in the germline. The excision of exons 4 and 5 results in a frameshift mutation that would lead to a premature termination even if the remaining exon 3 were to splice to exon 6. Exon 5 encodes the lysine residue necessary for catalytic activity. Western blot analyses using a polyclonal antibody did not detect protein in liver, muscle, and isolated adipocytes from homozygous mice.
Mutations Made By	Morris Birnbaum, Un of Pennsylvania Schl of Medicine

Disease/Phenotype

Disease Terms

Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

type 2 diabetes mellitus

Research Areas By Phenotype

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

Research Tools
- Diabetes and Obesity Research
- Metabolism Research
Diabetes and Obesity Research
- Insulin Resistance
- Hyperglycemia
- Type 2 Diabetes (NIDDM)

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Akt2^tm1.1Mbb/Akt2^tm1.1Mbb
involves: 129P2/OlaHsd * C57BL/6

adipose tissue phenotype

decreased adipocyte glucose uptake
- in euglycemic-hyperinsulinemic clamp studies, insulin-stimulated hexose uptake is mildly impaired in mutant adipocytes

muscle phenotype

decreased muscle cell glucose uptake
- insulin-stimulated hexose uptake into the glycolytic extensor digitorum longus (EDL) muscle is severely blunted in the presence of 0.33 nM insulin; however, no impairment is noted upon exposure of the mutant EDL to a higher insulin concentration (13.3 nM)
- Normal - insulin-stimulated deoxyglucose uptake into the oxidative soleus muscle is not significantly impaired at either an intermediate or maximal concentration of insulin

cellular phenotype

decreased muscle cell glucose uptake
- Normal - insulin-stimulated deoxyglucose uptake into the oxidative soleus muscle is not significantly impaired at either an intermediate or maximal concentration of insulin
- insulin-stimulated hexose uptake into the glycolytic extensor digitorum longus (EDL) muscle is severely blunted in the presence of 0.33 nM insulin; however, no impairment is noted upon exposure of the mutant EDL to a higher insulin concentration (13.3 nM)

decreased adipocyte glucose uptake
- in euglycemic-hyperinsulinemic clamp studies, insulin-stimulated hexose uptake is mildly impaired in mutant adipocytes

endocrine/exocrine gland phenotype

increased pancreatic islet number
- pancreata from 2- to 3-month-old male homozygotes respond to insulin resistance with an increase in islet mass (~4-fold) and number (~2-fold) relative to wild-type mice

homeostasis/metabolism phenotype

hyperglycemia
- homozygotes develop into adulthood without apparent growth defects but exhibit a mild but significant fasting hyperglycemia, which is more pronounced during fed states

insulin resistance
- Normal - however, circulating free fatty acid concentrations remain normal
- in euglycemic-hyperinsulinemic clamp expts, homozygotes exhibit peripheral insulin resistance along with complete failure of insulin to suppress hepatic glucose output
- in response to i.p. administration of insulin, homozygotes display significantly elevated blood glucose levels relative to wild-type mice at all time points measured (at 60 min; 70.8 ¿ 7.9 mg/dl vs 22.3 ¿ 1.1 mg/dl, respectively)
- notably, circulating free fatty acid concentrations remain normal

impaired glucose tolerance
- in response to oral glucose load, 2-mo-old homozygotes display a mild glucose intolerance, with increased blood glucose levels at all time points measured

increased circulating insulin level
- homozygotes develop inadequate compensatory hyperinsulinemia

Genotype: Akt2^tm1.1Mbb/Akt2^tm1.1Mbb
involves: 129P2/OlaHsd

homeostasis/metabolism phenotype

decreased liver triglyceride level
- 2-fold decrease in liver triglyceride levels

impaired glucose tolerance
- glucose intolerance

hyperglycemia
- about 25-30% increase in fasting glucose levels at 1 month of age

liver/biliary system phenotype

decreased liver triglyceride level
- 2-fold decrease in liver triglyceride levels

mammalian phenotype

immune system phenotype
- no abnormalities in T cell development are observed

The following phenotype relates to a compound genotype created using this strain

Genotype: Akt2^tm1.1Mbb/Akt2^tm1.1Mbb
B6.129P2-Akt2

growth/size/body region phenotype

decreased susceptibility to diet-induced obesity
- at 4 months when Surwit fed a high-fat diet

homeostasis/metabolism phenotype

decreased circulating glucose level
- in fasted mice Surwit fed a high-fat diet

decreased liver triglyceride level
- at 4 months when Surwit fed a high-fat diet

increased circulating insulin level
- in fasted mice Surwit fed a high-fat diet

decreased susceptibility to diet-induced obesity
- at 4 months when Surwit fed a high-fat diet

liver/biliary system phenotype

decreased liver triglyceride level
- at 4 months when Surwit fed a high-fat diet

References

Cho H; Mu J; Kim JK; Thorvaldsen JL; Chu Q; Crenshaw EB 3rd; Kaestner KH; Bartolomei MS; Shulman GI; Birnbaum MJ. 2001. Insulin resistance and a diabetes mellitus-like syndrome in mice lacking the protein kinase Akt2 (PKB beta). Science 292(5522):1728-31PubMed: 11387480 MGI: J:71491
Leavens KF; Easton RM; Shulman GI; Previs SF; Birnbaum MJ. 2009. Akt2 is required for hepatic lipid accumulation in models of insulin resistance. Cell Metab 10(5):405-18PubMed: 19883618 MGI: J:155432

Additional - Akt2^tm1.1Mbb related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Akt2
- Standard PCR:Akt2
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, heterozygous or homozygous mice can be bred. Homozygous mice may have impaired fecundity as a result of diabetic phenotype.
- Additional Breeding and Husbandry Support
Citation
When using the B6.129P2(Cg)-Akt2^tm1.1Mbb/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #006966 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

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
> >	Heterozygous or Wild-type for Cg-Akt2<tm1.1Mbb>

Related Products and Services

Frozen Mouse Embryo	B6.129P2(Cg)-Akt2<tm1.1Mbb>/J	$2595.00
Frozen Mouse Embryo	B6.129P2(Cg)-Akt2<tm1.1Mbb>/J	$2595.00
Frozen Mouse Embryo	B6.129P2(Cg)-Akt2<tm1.1Mbb>/J	$3373.50
Frozen Mouse Embryo	B6.129P2(Cg)-Akt2<tm1.1Mbb>/J	$3373.50

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.

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

Questions about Terms of Use

Additional Use Restrictions Apply

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

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Akt2tm1.1Mbb

Allele Symbol: Akt2tm1.1Mbb

Disease Terms

Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Akt2tm1.1Mbb/Akt2tm1.1Mbbinvolves: 129P2/OlaHsd * C57BL/6

adipose tissue phenotype

muscle phenotype

cellular phenotype

endocrine/exocrine gland phenotype

homeostasis/metabolism phenotype

Genotype: Akt2tm1.1Mbb/Akt2tm1.1Mbbinvolves: 129P2/OlaHsd

homeostasis/metabolism phenotype

liver/biliary system phenotype

mammalian phenotype

Genotype: Akt2tm1.1Mbb/Akt2tm1.1MbbB6.129P2-Akt2

growth/size/body region phenotype

homeostasis/metabolism phenotype

liver/biliary system phenotype

References

Additional - Akt2tm1.1Mbb related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

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

Live Mouse

Cryorecovery - Pricing

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Additional Use Restrictions Apply

Licensing Information

Akt2^tm1.1Mbb

Allele Symbol: Akt2^tm1.1Mbb

Genotype: Akt2^tm1.1Mbb/Akt2^tm1.1Mbb
involves: 129P2/OlaHsd * C57BL/6

Genotype: Akt2^tm1.1Mbb/Akt2^tm1.1Mbb
involves: 129P2/OlaHsd

Genotype: Akt2^tm1.1Mbb/Akt2^tm1.1Mbb
B6.129P2-Akt2

Additional - Akt2^tm1.1Mbb related