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 Heterozygote x +/+ sibling         (Female x Male)   19-NOV-08 Species laboratory mouse Generation N10+N1F1N1F13 (27-OCT-09)   Donating Investigator Morris Birnbaum,   Un of Pennsylvania Schl of Medicine

Description
Mice that are homozygous for the targeted mutation are viable and do not display any gross behavioral abnormalities. Homozygotes exhibit lower fertility. Female homozygotes do not nurse well; up to 50% perinatal mortality can occur. No gene product (mRNA or protein) is detected by Northern or Western blot analysis of mouse embryonic fibroblasts. Homozygotes are only 80% of wildtype body weight at birth, and remain small. This mutant mouse strain may be useful in related to organismal growth.

Development
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt exons 4 through 7 and the 5' end of exon 8. The construct was electroporated into 129P2Ola/Hsd derived E14 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric male animals were crossed to C57BL/6 mice, and then backcrossed to the same for 10 generations (March 2003).

Control Information

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

Additional Web Information

Genetic Quality Control Annual Report

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

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

Akt1^tm1Mbb/Akt1^tm1Mbb

        involves: 129P2/OlaHsd * C57BL/6

• lethality-postnatal
• postnatal lethality (MGI Ref ID J:72176)
  • normal numbers of homozygous embryos at E13.5
  • by 2-3 weeks after birth, fewer than expected numbers of homozygotes seen
  • significant numbers of deaths among homozygotes observed with first three days of life
  • survivors were fertile
• growth/size phenotype
• decreased body weight (MGI Ref ID J:72176)
  • 20% reduction in body weight at birth
  • at 14 months, homozygous males were only about 75% normal weight

View Research Applications

Research Applications

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

Akt1^tm1Mbb related

Cell Biology Research
Genes Regulating Growth and Proliferation

Developmental Biology Research
Growth Defects
      Growth Defects (homozygous)

Genes & Alleles

Gene & Allele Information

Allele Symbol		Akt1tm1Mbb
Allele Name		targeted mutation 1, Morris Birnbaum
Allele Type		Targeted (knock-out)
Common Name(s)		Akt-;
Mutation Made By		Morris Birnbaum,   Un of Pennsylvania Schl of Medicine
Strain of Origin		129P2/OlaHsd
ES Cell Line Name		E14
ES Cell Line Strain		129P2/OlaHsd
Gene Symbol and Name		Akt1, thymoma viral proto-oncogene 1
Chromosome		12
Gene Common Name(s)		AKT; MGC99656; PKB; PKB-ALPHA; PKB/Akt; PKBalpha; PRKBA; RAC; RAC-ALPHA;
Molecular Note		A neomycin resistance gene was used to replace exons 4 through 7 and the 5' portion of exon 8. Exon 5 is known to encode an lysine residue essential for catalytic activity. Expression was undetected in homozygous mutant animals by both Northern and Western blot analyses. The authors noted that the expression of Akt2 and Akt3 was normal in mice homozygous for the targeted allele. [MGI Ref ID J:72176]

Genotyping

Genotyping Information

Genotyping Protocols

Akt1^tm1Mbb, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References

Selected Reference(s)

Cho H; Thorvaldsen JL; Chu Q; Feng F; Birnbaum MJ. 2001. Akt1/pkbalpha is required for normal growth but dispensable for maintenance of glucose homeostasis in mice. J Biol Chem 276(42):38349-52. [PubMed: 11533044]  [MGI Ref ID J:72176]

Additional References

Akt1^tm1Mbb related

Ackah E; Yu J; Zoellner S; Iwakiri Y; Skurk C; Shibata R; Ouchi N; Easton RM; Galasso G; Birnbaum MJ; Walsh K; Sessa WC. 2005. Akt1/protein kinase Balpha is critical for ischemic and VEGF-mediated angiogenesis. J Clin Invest 115(8):2119-2127. [PubMed: 16075056]  [MGI Ref ID J:100143]

Boxer RB; Stairs DB; Dugan KD; Notarfrancesco KL; Portocarrero CP; Keister BA; Belka GK; Cho H; Rathmell JC; Thompson CB; Birnbaum MJ; Chodosh LA. 2006. Isoform-specific requirement for Akt1 in the developmental regulation of cellular metabolism during lactation. Cell Metab 4(6):475-90. [PubMed: 17141631]  [MGI Ref ID J:129773]

DeBosch B; Sambandam N; Weinheimer C; Courtois M; Muslin AJ. 2006. Akt2 regulates cardiac metabolism and cardiomyocyte survival. J Biol Chem 281(43):32841-51. [PubMed: 16950770]  [MGI Ref ID J:117383]

DeBosch B; Treskov I; Lupu TS; Weinheimer C; Kovacs A; Courtois M; Muslin AJ. 2006. Akt1 is required for physiological cardiac growth. Circulation 113(17):2097-104. [PubMed: 16636172]  [MGI Ref ID J:122451]

Dickey CA; Koren J; Zhang YJ; Xu YF; Jinwal UK; Birnbaum MJ; Monks B; Sun M; Cheng JQ; Patterson C; Bailey RM; Dunmore J; Soresh S; Leon C; Morgan D; Petrucelli L. 2008. Akt and CHIP coregulate tau degradation through coordinated interactions. Proc Natl Acad Sci U S A 105(9):3622-7. [PubMed: 18292230]  [MGI Ref ID J:132677]

Easton RM; Cho H; Roovers K; Shineman DW; Mizrahi M; Forman MS; Lee VM; Szabolcs M; de Jong R; Oltersdorf T; Ludwig T; Efstratiadis A; Birnbaum MJ. 2005. Role for Akt3/protein kinase Bgamma in attainment of normal brain size. Mol Cell Biol 25(5):1869-78. [PubMed: 15713641]  [MGI Ref ID J:96823]

Fernandez-Hernando C; Ackah E; Yu J; Suarez Y; Murata T; Iwakiri Y; Prendergast J; Miao RQ; Birnbaum MJ; Sessa WC. 2007. Loss of akt1 leads to severe atherosclerosis and occlusive coronary artery disease. Cell Metab 6(6):446-57. [PubMed: 18054314]  [MGI Ref ID J:130443]

Hammerman PS; Fox CJ; Birnbaum MJ; Thompson CB. 2005. Pim and Akt oncogenes are independent regulators of hematopoietic cell growth and survival. Blood 105(11):4477-83. [PubMed: 15705789]  [MGI Ref ID J:98472]

Jacobs SR; Herman CE; Maciver NJ; Wofford JA; Wieman HL; Hammen JJ; Rathmell JC. 2008. Glucose Uptake Is Limiting in T Cell Activation and Requires CD28-Mediated Akt-Dependent and Independent Pathways. J Immunol 180(7):4476-86. [PubMed: 18354169]  [MGI Ref ID J:132993]

Jee HJ; Kim HJ; Kim AJ; Bae YS; Bae SS; Yun J. 2009. UV light induces premature senescence in Akt1-null mouse embryonic fibroblasts by increasing intracellular levels of ROS. Biochem Biophys Res Commun 383(3):358-62. [PubMed: 19364500]  [MGI Ref ID J:149681]

Jorgensen ND; Andresen JM; Lagalwar S; Armstrong B; Stevens S; Byam CE; Duvick LA; Lai S; Jafar-Nejad P; Zoghbi HY; Clark HB; Orr HT. 2009. Phosphorylation of ATXN1 at Ser776 in the cerebellum. J Neurochem 110(2):675-86. [PubMed: 19500214]  [MGI Ref ID J:150968]

Kiessling S; Lutz-Nicoladoni C; Olsson A; Niederegger H; Baier G; Villunger A. 2007. Compensatory mechanisms regulate the Bcl-2 rheostat and lymphocyte survival in the absence of AKT1/PKBalpha. Cell Death Differ 14(1):186-9. [PubMed: 16778831]  [MGI Ref ID J:132346]

Lai WS; Xu B; Westphal KG; Paterlini M; Olivier B; Pavlidis P; Karayiorgou M; Gogos JA. 2006. Akt1 deficiency affects neuronal morphology and predisposes to abnormalities in prefrontal cortex functioning. Proc Natl Acad Sci U S A 103(45):16906-11. [PubMed: 17077150]  [MGI Ref ID J:117100]

Li D; August S; Woulfe DS. 2008. GSK3beta is a negative regulator of platelet function and thrombosis. Blood 111(7):3522-30. [PubMed: 18218855]  [MGI Ref ID J:133503]

Li G; Anderson RE; Tomita H; Adler R; Liu X; Zack DJ; Rajala RV. 2007. Nonredundant role of Akt2 for neuroprotection of rod photoreceptor cells from light-induced cell death. J Neurosci 27(1):203-11. [PubMed: 17202487]  [MGI Ref ID J:117208]

Mogi M; Yang J; Lambert JF; Colvin GA; Shiojima I; Skurk C; Summer R; Fine A; Quesenberry PJ; Walsh K. 2003. Akt signaling regulates side population cell phenotype via Bcrp1 translocation. J Biol Chem 278(40):39068-75. [PubMed: 12851395]  [MGI Ref ID J:132379]

Nishi J; Minamino T; Miyauchi H; Nojima A; Tateno K; Okada S; Orimo M; Moriya J; Fong GH; Sunagawa K; Shibuya M; Komuro I. 2008. Vascular endothelial growth factor receptor-1 regulates postnatal angiogenesis through inhibition of the excessive activation of Akt. Circ Res 103(3):261-8. [PubMed: 18583712]  [MGI Ref ID J:151369]

Phung TL; Ziv K; Dabydeen D; Eyiah-Mensah G; Riveros M; Perruzzi C; Sun J; Monahan-Earley RA; Shiojima I; Nagy JA; Lin MI; Walsh K; Dvorak AM; Briscoe DM; Neeman M; Sessa WC; Dvorak HF; Benjamin LE. 2006. Pathological angiogenesis is induced by sustained Akt signaling and inhibited by rapamycin. Cancer Cell 10(2):159-70. [PubMed: 16904613]  [MGI Ref ID J:112695]

Rasoulpour T; DiPalma K; Kolvek B; Hixon M. 2006. Akt1 suppresses radiation-induced germ cell apoptosis in vivo. Endocrinology 147(9):4213-21. [PubMed: 16763066]  [MGI Ref ID J:129523]

Rogers R; Ouellet G; Brown C; Moyer B; Rasoulpour T; Hixon M. 2008. Cross-talk between the Akt and NF-kappaB signaling pathways inhibits MEHP-induced germ cell apoptosis. Toxicol Sci 106(2):497-508. [PubMed: 18755736]  [MGI Ref ID J:142547]

Wofford JA; Wieman HL; Jacobs SR; Zhao Y; Rathmell JC. 2008. IL-7 promotes Glut1 trafficking and glucose uptake via STAT5-mediated activation of Akt to support T-cell survival. Blood 111(4):2101-11. [PubMed: 18042802]  [MGI Ref ID J:131334]

Woulfe D; Jiang H; Morgans A; Monks R; Birnbaum M; Brass LF. 2004. Defects in secretion, aggregation, and thrombus formation in platelets from mice lacking Akt2. J Clin Invest 113(3):441-50. [PubMed: 14755341]  [MGI Ref ID J:87588]

Xin X; Chen S; Khan ZA; Chakrabarti S. 2007. Akt activation and augmented fibronectin production in hyperhexosemia. Am J Physiol Endocrinol Metab 293(4):E1036-44. [PubMed: 17666488]  [MGI Ref ID J:125528]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX12

Colony Maintenance

Breeding & Husbandry	This strain originated on a B6;129 background and has been backcrossed to C57BL/6 for at least 10 generations (March 2003). The strain is maintained as a heterozygote. Homozygotes are reported to be less fertile. Female homozygotes do not nurse well; up to 50% perinatal mortality can occur.
Mating System	Heterozygote x +/+ sibling         (Female x Male)   19-NOV-08
Diet Information	LabDiet® 5K52/5K67

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

Standard Supply

Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of approximately nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within two business days following order placement.

Supply Notes

Usually shipped between four and eight weeks of age. This strain is included in the Induced Mutant Resource Colony collection. Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	Wild-type from the colony
	000664 C57BL/6J
Considerations for Choosing Controls
USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains.
International - Control Pricing Information for Genetically Engineered Mutant Strains.

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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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Contact information

General inquiries

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phone:	207-288-6470
fax:	207-288-6655

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