Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Type Coisogenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse Generation F?+N1F2pN1 Generation Definitions   Donating Investigator Andreas Strasser,   Walter and Eliza Hall Inst of Med Res

Description
Mice that are homozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. No gene product (mRNA) is detected by RT-PCR analysis of irradiated thymocytes from homozygotes and Northern blot analysis of testis, lung and spleen from homozygotes. Thymocytes from homozygous mice exhibit increased resistance to DNA-damage induced apoptosis after treatment by etoposide. NK cells from homozygotes survive better than wildtype controls when cultured without IL-15.

Development
A targeting vector containing a floxed PGK-hygromycin cassette was used to disrupt exons 2 and 3, which encode the 2 BH3 domains. The construct was electroporated into C57BL/6 derived Bruce4 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric animals were crossed to mice expressing Cre recombinase, on the C57BL/6 background, to remove the selection cassette. Upon arrival at The Jackson Laboratory the mice were crossed once to C57BL/6J to establish the colony.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

Pmaip1^tm1Ast/Pmaip1^tm1Ast

        C57BL/6-Pmaip1^tm1Ast

• cellular phenotype
• decreased sensitivity to induced cell death
  • modest but significant resistance to etoposide induced apoptosis in mouse embryo fibroblasts but not in thymocytes and other lymphocytes   (MGI Ref ID J:86466)
• immune system phenotype
• abnormal NK cell morphology
  • following expansion in culture, NK cells survive IL-15 withdrawal better than wild-type cells   (MGI Ref ID J:123409)
• hematopoietic system phenotype
• abnormal NK cell morphology
  • following expansion in culture, NK cells survive IL-15 withdrawal better than wild-type cells   (MGI Ref ID J:123409)

Pmaip1^tm1Ast/Pmaip1^tm1Ast

        involves: C57BL/6

• immune system phenotype
• *normal* immune system phenotype
  • no abnormalities are detected in T cell numbers after HSV-1 infection   (MGI Ref ID J:132819)
• nervous system phenotype
• *normal* nervous system phenotype
  • unlike mice homozygous for Bbc3^tm1Ast neuron sensitivity to oxidative stressor induced apoptosis is similar to controls   (MGI Ref ID J:127640)

View Research Applications

Research Applications

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

Apoptosis Research

Cancer Research
Other
      DNA Repair

Cell Biology Research
DNA Damage Response

Research Tools
Apoptosis Research
Immunology and Inflammation Research

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Pmaip1tm1Ast
Allele Name		targeted mutation 1, Andreas Strasser
Allele Type		Targeted (knock-out)
Common Name(s)		noxa-;
Mutation Made By		Andreas Strasser,   Walter and Eliza Hall Inst of Med Res
Strain of Origin		B6.Cg-Thy1
Gene Symbol and Name		Pmaip1, phorbol-12-myristate-13-acetate-induced protein 1
Chromosome		18
Gene Common Name(s)		Noxa;
Molecular Note		Exons 2 and 3 which contain the two BH3 interaction domains were replaced with a floxed PGK-hygromycin resistance cassette. The resistance gene was excised in vivo by crossing to C57BL/6 Deleter mice. Gene disruption was confirmed by RT-PCR and by Northern blot analysis. [MGI Ref ID J:86466]

Genotyping

Genotyping Information

Genotyping Protocols

Pmaip1^tm1Ast, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Villunger A; Michalak EM; Coultas L; Mullauer F; Bock G; Ausserlechner MJ; Adams JM; Strasser A. 2003. p53- and drug-induced apoptotic responses mediated by BH3-only proteins puma and noxa. Science 302(5647):1036-8. [PubMed: 14500851]  [MGI Ref ID J:86466]

Additional References

Pmaip1^tm1Ast related

Akhtar RS; Geng Y; Klocke BJ; Latham CB; Villunger A; Michalak EM; Strasser A; Carroll SL; Roth KA. 2006. BH3-only proapoptotic Bcl-2 family members Noxa and Puma mediate neural precursor cell death. J Neurosci 26(27):7257-64. [PubMed: 16822983]  [MGI Ref ID J:110228]

Bauer A; Villunger A; Labi V; Fischer SF; Strasser A; Wagner H; Schmid RM; Hacker G. 2006. The NF-kappaB regulator Bcl-3 and the BH3-only proteins Bim and Puma control the death of activated T cells. Proc Natl Acad Sci U S A 103(29):10979-84. [PubMed: 16832056]  [MGI Ref ID J:111822]

Chang KC; Unsinger J; Davis CG; Schwulst SJ; Muenzer JT; Strasser A; Hotchkiss RS. 2007. Multiple triggers of cell death in sepsis: death receptor and mitochondrial-mediated apoptosis. FASEB J 21(3):708-19. [PubMed: 17307841]  [MGI Ref ID J:134855]

Ekoff M; Kaufmann T; Engstrom M; Motoyama N; Villunger A; Jonsson JI; Strasser A; Nilsson G. 2007. The BH3-only protein Puma plays an essential role in cytokine deprivation induced apoptosis of mast cells. Blood 110(9):3209-17. [PubMed: 17634411]  [MGI Ref ID J:149129]

Erlacher M; Michalak EM; Kelly PN; Labi V; Niederegger H; Coultas L; Adams JM; Strasser A; Villunger A. 2005. BH3-only proteins Puma and Bim are rate-limiting for gamma-radiation- and glucocorticoid-induced apoptosis of lymphoid cells in vivo. Blood 106(13):4131-8. [PubMed: 16118324]  [MGI Ref ID J:124060]

Fischer SF; Belz GT; Strasser A. 2008. BH3-only protein Puma contributes to death of antigen-specific T cells during shutdown of an immune response to acute viral infection. Proc Natl Acad Sci U S A 105(8):3035-40. [PubMed: 18287039]  [MGI Ref ID J:132819]

Gray DH; Kupresanin F; Berzins SP; Herold MJ; O'Reilly LA; Bouillet P; Strasser A. 2012. The BH3-Only Proteins Bim and Puma Cooperate to Impose Deletional Tolerance of Organ-Specific Antigens. Immunity 37(3):451-62. [PubMed: 22960223]  [MGI Ref ID J:187669]

Happo L; Cragg MS; Phipson B; Haga JM; Jansen ES; Herold MJ; Dewson G; Michalak EM; Vandenberg CJ; Smyth GK; Strasser A; Cory S; Scott CL. 2010. Maximal killing of lymphoma cells by DNA damage-inducing therapy requires not only the p53 targets Puma and Noxa, but also Bim. Blood 116(24):5256-67. [PubMed: 20829369]  [MGI Ref ID J:167411]

Huntington ND; Puthalakath H; Gunn P; Naik E; Michalak EM; Smyth MJ; Tabarias H; Degli-Esposti MA; Dewson G; Willis SN; Motoyama N; Huang DC; Nutt SL; Tarlinton DM; Strasser A. 2007. Interleukin 15-mediated survival of natural killer cells is determined by interactions among Bim, Noxa and Mcl-1. Nat Immunol 8(8):856-863. [PubMed: 17618288]  [MGI Ref ID J:123409]

Kerr JB; Hutt KJ; Michalak EM; Cook M; Vandenberg CJ; Liew SH; Bouillet P; Mills A; Scott CL; Findlay JK; Strasser A. 2012. DNA damage-induced primordial follicle oocyte apoptosis and loss of fertility require TAp63-mediated induction of Puma and Noxa. Mol Cell 48(3):343-52. [PubMed: 23000175]  [MGI Ref ID J:191005]

McKenzie MD; Jamieson E; Jansen ES; Scott CL; Huang DC; Bouillet P; Allison J; Kay TW; Strasser A; Thomas HE. 2010. Glucose induces pancreatic islet cell apoptosis that requires the BH3-only proteins Bim and Puma and multi-BH domain protein Bax. Diabetes 59(3):644-52. [PubMed: 19959756]  [MGI Ref ID J:164154]

Merino D; Khaw SL; Glaser SP; Anderson DJ; Belmont LD; Wong C; Yue P; Robati M; Phipson B; Fairlie WD; Lee EF; Campbell KJ; Vandenberg CJ; Cory S; Roberts AW; Ludlam MJ; Huang DC; Bouillet P. 2012. Bcl-2, Bcl-x(L), and Bcl-w are not equivalent targets of ABT-737 and navitoclax (ABT-263) in lymphoid and leukemic cells. Blood 119(24):5807-16. [PubMed: 22538851]  [MGI Ref ID J:188645]

Michalak EM; Jansen ES; Happo L; Cragg MS; Tai L; Smyth GK; Strasser A; Adams JM; Scott CL. 2009. Puma and to a lesser extent Noxa are suppressors of Myc-induced lymphomagenesis. Cell Death Differ 16(5):684-96. [PubMed: 19148184]  [MGI Ref ID J:164197]

Michalak EM; Villunger A; Adams JM; Strasser A. 2008. In several cell types tumour suppressor p53 induces apoptosis largely via Puma but Noxa can contribute. Cell Death Differ 15(6):1019-29. [PubMed: 18259198]  [MGI Ref ID J:149036]

Naik E; Michalak EM; Villunger A; Adams JM; Strasser A. 2007. Ultraviolet radiation triggers apoptosis of fibroblasts and skin keratinocytes mainly via the BH3-only protein Noxa. J Cell Biol 176(4):415-24. [PubMed: 17283183]  [MGI Ref ID J:119726]

Santidrian AF; Gonzalez-Girones DM; Iglesias-Serret D; Coll-Mulet L; Cosialls AM; de Frias M; Campas C; Gonzalez-Barca E; Alonso E; Labi V; Viollet B; Benito A; Pons G; Villunger A; Gil J. 2010. AICAR induces apoptosis independently of AMPK and p53 through up-regulation of the BH3-only proteins BIM and NOXA in chronic lymphocytic leukemia cells. Blood 116(16):3023-32. [PubMed: 20664053]  [MGI Ref ID J:165862]

Steckley D; Karajgikar M; Dale LB; Fuerth B; Swan P; Drummond-Main C; Poulter MO; Ferguson SS; Strasser A; Cregan SP. 2007. Puma is a dominant regulator of oxidative stress induced Bax activation and neuronal apoptosis. J Neurosci 27(47):12989-99. [PubMed: 18032672]  [MGI Ref ID J:127640]

Urich D; Soberanes S; Burgess Z; Chiarella SE; Ghio AJ; Ridge KM; Kamp DW; Chandel NS; Mutlu GM; Budinger GR. 2009. Proapoptotic Noxa is required for particulate matter-induced cell death and lung inflammation. FASEB J 23(7):2055-64. [PubMed: 19237507]  [MGI Ref ID J:150539]

Wensveen FM; Derks IA; van Gisbergen KP; de Bruin AM; Meijers JC; Yigittop H; Nolte MA; Eldering E; van Lier RA. 2012. BH3-only protein Noxa regulates apoptosis in activated B cells and controls high-affinity antibody formation. Blood 119(6):1440-9. [PubMed: 22144184]  [MGI Ref ID J:181744]

Wensveen FM; Klarenbeek PL; van Gisbergen KP; Pascutti MF; Derks IA; van Schaik BD; Ten Brinke A; de Vries N; Cekinovic D; Jonjic S; van Lier RA; Eldering E. 2013. Pro-apoptotic protein Noxa regulates memory T cell population size and protects against lethal immunopathology. J Immunol 190(3):1180-91. [PubMed: 23277490]  [MGI Ref ID J:193027]

Wensveen FM; van Gisbergen KP; Derks IA; Gerlach C; Schumacher TN; van Lier RA; Eldering E. 2010. Apoptosis threshold set by Noxa and Mcl-1 after T cell activation regulates competitive selection of high-affinity clones. Immunity 32(6):754-65. [PubMed: 20620942]  [MGI Ref ID J:162395]

Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Animal Health Reports

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

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, these mice can be bred as homozygotes.

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.

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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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