Description

Strain Information

Type Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Mating System Heterozygote x Heterozygote         (Female x Male) Species laboratory mouse Generation N6+N1F3 (17-JUL-07)   Donating Investigator Anthony Wynshaw-Boris,   UCSD

Appearance
white-bellied agouti, ataxic
Related Genotype: A^w/A^w Atm^tm1Awb/Atm^tm1Awb

Description
Mice homozygous for the Atm^tm1Awb targeted mutation display many of the characteristics of ataxia telangiectasia, including growth retardation, neurologic dysfunction, infertility, defects in T lymphocyte maturation, and extreme sensitivity to gamma-irradiation. Most homozygotes develop thymic lymphoma between 2 and 4 months of age. Heterozygous mice display no abnormalities through eight months of age.

Development
This strain was developed in the laboratory of Dr. Anthony Wynshaw-Boris at the National Institutes of Health. The Atm gene was disrupted by using an insertion vector containing the neo resistance gene to produce a truncation mutation at approximately the site corresponding to that commonly mutated in ATM in many human beings with ataxia telangiectasia (AT).

Control Information

	Control
	Wild-type from the colony
Considerations for Choosing Controls

Additional Web Information

New 129 Nomenclature Bulletin

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms

Ataxia-Telangiectasia; AT - Models with phenotypic similarity to human disease where etiologies involve orthologs.1

1 Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

Atm^tm1Awb/Atm^tm1Awb

        involves: 129S6/SvEvTac

• cellular phenotype
• *normal* cellular phenotype (MGI Ref ID J:126186)
  • mouse embryonic fibroblast cells arrest and undergo apoptosis following exposure to ionizing radiation

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

Atm^tm1Awb/Atm^tm1Awb

        either: 129S6/SvEvTac-Atm^tm1Awb or (involves: 129S6/SvEvTac * NIH Black Swiss)

• life span-post-weaning/aging
• increased mortality induced by gamma-irradiation (MGI Ref ID J:34193)
  • mutant mice die from radiation induced toxicity to the gastrointestinal tract at doses that do not kill control mice
• premature death (MGI Ref ID J:34193)
  • many mice die from thymic lymphoma; none survived greater than 4.5 months of age without a thymic lymphoma
• growth/size phenotype
• decreased body size (MGI Ref ID J:34193)
  • homozygotes appear smaller at birth
• decreased body weight (MGI Ref ID J:34193)
  • female and male homozygotes weigh less that control littermates from P8 to 3 months of age
• immune system phenotype
• *normal* immune system phenotype (MGI Ref ID J:34193)
  • no abnormalities in B lymphocytes, granulocytes or myeloid cells observed
• decreased T cell number (MGI Ref ID J:34193)
  • reduced number of mature single-positive Cd4+ and Cd8+ T lymphocytes
• decreased activated T cell number (MGI Ref ID J:34193)
  • using Cd69 as a marker of activation, the number of Cd3/Cd69 or Cd8/Cd69 positive cells is reduced, but still present
• decreased double-positive T cell number (MGI Ref ID J:34193)
  • 59% reduction in Cd3/Cd4 double positive T lymphocytes
  • 67% reduction in Cd3/Cd8 double positive T lymphocytes
  • reduction in Cd5, Cd4, and Cd8 positive T lymphocytes
• increased double-positive T cell number (MGI Ref ID J:34193)
  • increased number of immature double positive cells
• reproductive system phenotype
• abnormal female reproductive anatomy (MGI Ref ID J:34193)
• abnormal uterus morphology (MGI Ref ID J:34193)
  • no proliferation or degeneration in as part of the estrous cycle
• absent ovarian follicles (MGI Ref ID J:34193)
  • absence of primordial and mature ovarian follicles
• small ovary (MGI Ref ID J:34193)
• abnormal gametogenesis (MGI Ref ID J:34193)
• absent oocytes (MGI Ref ID J:34193)
  • complete absence of mature gametes
• arrest of spermatogenesis (MGI Ref ID J:34193)
• azoospermia (MGI Ref ID J:34193)
  • absence of mature sperm
• abnormal male reproductive anatomy (MGI Ref ID J:34193)
• abnormal seminiferous tubule morphology (MGI Ref ID J:34193)
  • reduced number of cells
  • degeneration of cells evident
  • some barren of all cells except Sertoli cells
• small testis (MGI Ref ID J:34193)
• abnormal reproductive system physiology (MGI Ref ID J:34193)
• absent estrous (MGI Ref ID J:34193)
  • females never enter estrous
• female infertility (MGI Ref ID J:34193)
  • females never exhibit copulation plugs
• male infertility (MGI Ref ID J:34193)
  • normal mating behavior evident by the presence of copulation plugs in control females; however, pregnancy never results
• tumorigenesis
• T cell derived lymphoma (MGI Ref ID J:34193)
  • thymic lymphomas are highly metastatic and consist of immature T cells
• thymic lymphoma (MGI Ref ID J:34193)
  • thymic lymphoblastic lymphomas develop in 100% of mice between 2-4.5 months of age
  • rapid tumor growth may cause death from compression of other internal organs
  • rapid tumor growth may cause death from compression of other internal organs
• cellular phenotype
• abnormal cell physiology (MGI Ref ID J:34193)
  • mutant fibroblasts grew more slowly in culture than control cells
• abnormal cell cycle (MGI Ref ID J:34193)
• increased cellular sensitivity to gamma-irradiation (MGI Ref ID J:34193)
  • mutant fibroblasts show increased radioresistant DNA synthesis (RDS) after 5 to 15 Gy of gamma-irradiation compared to controls, indicating that cell cycle checkpoints are abnormal
• oxidative stress (MGI Ref ID J:57115)
  • tissues from mutants are under oxidative stress and suffer oxidative damage, especially in the brain
  • oxidative damage to proteins and lipids as indicated by elevated nitrotyrosine levels in the brain (but not the liver) and elevated F2-isoprostanes in the testes (indicative of lipid damage)
  • activity of the isozyme, heme oxygenase, is increased 600% in the cerebellum (but not in the cortex)
• abnormal lysosome morphology (MGI Ref ID J:59933)
  • significant increase in the number of lysosomes in cerebellar Purkinje cells and in pyramidal cells of the hippocampus in the absence of any neuronal degeneration at 4-12 weeks of age, before the onset of T cell lymphoma
• behavior/neurological phenotype
• decreased vertical activity (MGI Ref ID J:34193)
  • mutant mice reared less often than controls
• hypoactivity (MGI Ref ID J:34193)
  • reduced horizontal activity was shown by reduced movement around an open field
• impaired coordination (MGI Ref ID J:34193)
  • mutant mice were not able to stay on a rota-rod as long as controls
  • impaired performance was not due to decreased strength since mice were able to suspend from a wire lid as long as controls
• short stride length (MGI Ref ID J:34193)
  • in addition, the maximum difference in stride lengths was greater in mutant mice, suggestive of ataxia
• nervous system phenotype
• *normal* nervous system phenotype (MGI Ref ID J:34193)
  • no defects in brain architecture
  • no evidence of neurodegeneration
• abnormal Purkinje cell morphology (MGI Ref ID J:57115)
  • heme oxygenase 1 is increase in Purkinje cells, indicating oxidative damage particularly in these cells
• hematopoietic system phenotype
• decreased T cell number (MGI Ref ID J:34193)
  • reduced number of mature single-positive Cd4+ and Cd8+ T lymphocytes
• decreased activated T cell number (MGI Ref ID J:34193)
  • using Cd69 as a marker of activation, the number of Cd3/Cd69 or Cd8/Cd69 positive cells is reduced, but still present
• decreased double-positive T cell number (MGI Ref ID J:34193)
  • 59% reduction in Cd3/Cd4 double positive T lymphocytes
  • 67% reduction in Cd3/Cd8 double positive T lymphocytes
  • reduction in Cd5, Cd4, and Cd8 positive T lymphocytes
• increased double-positive T cell number (MGI Ref ID J:34193)
  • increased number of immature double positive cells
• endocrine/exocrine gland phenotype
• abnormal seminiferous tubule morphology (MGI Ref ID J:34193)
  • reduced number of cells
  • degeneration of cells evident
  • some barren of all cells except Sertoli cells
• absent ovarian follicles (MGI Ref ID J:34193)
  • absence of primordial and mature ovarian follicles
• small ovary (MGI Ref ID J:34193)
• small testis (MGI Ref ID J:34193)

Atm^tm1Awb/Atm^tm1Awb

        involves: 129S6/SvEvTac * C57BL/6

• life span-post-weaning/aging
• premature death (MGI Ref ID J:103922)
  • majority die with thymic lymphomas by 5 months of age, 2.9% live up to 10 months, and none live beyond 15 months
• tumorigenesis
• thymic lymphoma (MGI Ref ID J:103922)
  • majority die with thymic lymphomas
• cellular phenotype
• abnormal cell cycle checkpoint function (MGI Ref ID J:103922)
  • MEFs exhibit defects in G1/S, intra-S-phase, and G2/M checkpoints after ionizing radiation induced DNA damage
• chromosome breakage (MGI Ref ID J:103922)

View Research Applications

Research Applications

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

Atm^tm1Awb related

Cancer Research
Increased Tumor Incidence (Lymphomas: thymic)
Tumor Suppressor Genes

Immunology and Inflammation Research
Immunodeficiency Associated with Other Defects

Mouse/Human Gene Homologs
ataxia telangiectasia

Neurobiology Research
Ataxia (Movement) Defects
Neurodevelopmental Defects

Reproductive Biology Research
Fertility Defects

Genes & Alleles

Gene & Allele Information

Allele Symbol		Atmtm1Awb
Allele Name		targeted mutation 1, Anthony Wynshaw Boris
Allele Type		Targeted (knock-out)
Common Name(s)		Atm-; Atmins5790neo; Atmtm1Awbl;
Mutation Made By		Anthony Wynshaw-Boris,   UCSD
Strain of Origin		129S6/SvEvTac
ES Cell Line Name		TC-1
ES Cell Line Strain		129S6/SvEvTac
Gene Symbol and Name		Atm, ataxia telangiectasia mutated homolog (human)
Chromosome		9
Gene Common Name(s)		AI256621; AT1; ATA; ATC; ATD; ATDC; ATE; C030026E19Rik; DKFZp781A0353; MGC74674; RIKEN cDNA C030026E19 gene; TEL1; TELO1; expressed sequence AI256621;
Molecular Note		A PGK-neomycin cassette was inserted into position 5979 of the Atm gene. This mutation results in a truncated protein, and the position of the mutation corresponds to the location of truncation mutations known to exist in humans. [MGI Ref ID J:34193]

Genotyping

Genotyping Information

Genotyping Protocols

Atm^tm1Awb, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Barlow C; Hirotsune S; Paylor R; Liyanage M; Eckhaus M; Collins F; Shiloh Y; Crawley JN; Ried T; Tagle D; Wynshaw-Boris A. 1996. Atm-deficient mice: a paradigm of ataxia telangiectasia. Cell 86(1):159-71. [PubMed: 8689683]  [MGI Ref ID J:34193]

Additional References

Macleod MR; Ramage L; McGregor A; Seckl JR. 2003. Reduced NMDA-induced apoptosis in neurons lacking ataxia telangiectasia mutated protein. Neuroreport 14(2):215-7. [PubMed: 12598732]  [MGI Ref ID J:89866]

Shackelford RE; Manuszak RP; Johnson CD; Hellrung DJ; Link CJ; Wang S. 2004. Iron chelators increase the resistance of Ataxia telangeictasia cells to oxidative stress. DNA Repair (Amst) 3(10):1263-72. [PubMed: 15336622]  [MGI Ref ID J:92530]

Smilenov LB; Brenner DJ; Hall EJ. 2001. Modest increased sensitivity to radiation oncogenesis in ATM heterozygous versus wild-type mammalian cells. Cancer Res 61(15):5710-3. [PubMed: 11479203]  [MGI Ref ID J:70725]

Weil MM; Kittrell FS; Yu Y; McCarthy M; Zabriskie RC; Ullrich RL. 2001. Radiation induces genomic instability and mammary ductal dysplasia in Atm heterozygous mice. Oncogene 20(32):4409-11. [PubMed: 11466622]  [MGI Ref ID J:70611]

Yan M; Kuang X; Qiang W; Shen J; Claypool K; Lynn WS; Wong PK. 2002. Prevention of thymic lymphoma development in atm-/- mice by dexamethasone. Cancer Res 62(18):5153-7. [PubMed: 12234978]  [MGI Ref ID J:79018]

Atm^tm1Awb related

Aleyasin H; Cregan SP; Iyirhiaro G; O'Hare MJ; Callaghan SM; Slack RS; Park DS. 2004. Nuclear factor-(kappa)B modulates the p53 response in neurons exposed to DNA damage. J Neurosci 24(12):2963-73. [PubMed: 15044535]  [MGI Ref ID J:90221]

Allen DM; van Praag H; Ray J; Weaver Z; Winrow CJ; Carter TA; Braquet R; Harrington E; Ried T; Brown KD; Gage FH; Barlow C. 2001. Ataxia telangiectasia mutated is essential during adult neurogenesis. Genes Dev 15(5):554-66. [PubMed: 11238376]  [MGI Ref ID J:68085]

Bagley J; Cortes ML; Breakefield XO; Iacomini J. 2004. Bone marrow transplantation restores immune system function and prevents lymphoma in Atm-deficient mice. Blood 104(2):572-8. [PubMed: 15044255]  [MGI Ref ID J:92237]

Bailey SL; Gurley KE; Hoon-Kim K; Kelly-Spratt KS; Kemp CJ. 2008. Tumor suppression by p53 in the absence of Atm. Mol Cancer Res 6(7):1185-92. [PubMed: 18583527]  [MGI Ref ID J:139874]

Barchi M; Mahadevaiah S; Di Giacomo M; Baudat F; de Rooij DG; Burgoyne PS; Jasin M; Keeney S. 2005. Surveillance of different recombination defects in mouse spermatocytes yields distinct responses despite elimination at an identical developmental stage. Mol Cell Biol 25(16):7203-15. [PubMed: 16055729]  [MGI Ref ID J:133053]

Barchi M; Roig I; Di Giacomo M; de Rooij DG; Keeney S; Jasin M. 2008. ATM promotes the obligate XY crossover and both crossover control and chromosome axis integrity on autosomes. PLoS Genet 4(5):e1000076. [PubMed: 18497861]  [MGI Ref ID J:137071]

Barlow C; Brown KD; Deng CX; Tagle DA; Wynshaw-Boris A. 1997. Atm selectively regulates distinct p53-dependent cell-cycle checkpoint and apoptotic pathways. Nat Genet 17(4):453-6. [PubMed: 9398849]  [MGI Ref ID J:76690]

Barlow C; Dennery PA; Shigenaga MK; Smith MA; Morrow JD; Roberts LJ 2nd; Wynshaw-Boris A; Levine RL. 1999. Loss of the ataxia-telangiectasia gene product causes oxidative damage in target organs. Proc Natl Acad Sci U S A 96(17):9915-9. [PubMed: 10449794]  [MGI Ref ID J:57115]

Barlow C; Liyanage M; Moens PB; Deng CX; Ried T; Wynshaw-Boris A. 1997. Partial rescue of the prophase I defects of Atm-deficient mice by p53 and p21 null alleles. Nat Genet 17(4):462-6. [PubMed: 9398851]  [MGI Ref ID J:44388]

Barlow C; Liyanage M; Moens PB; Tarsounas M; Nagashima K; Brown K; Rottinghaus S; Jackson SP; Tagle D; Ried T; Wynshaw-Boris A. 1998. Atm deficiency results in severe meiotic disruption as early as leptonema of prophase I. Development 125(20):4007-17. [PubMed: 9735362]  [MGI Ref ID J:51058]

Barlow C; Ribaut-Barassin C; Zwingman TA; Pope AJ; Brown KD; Owens JW; Larson D; Harrington EA; Haeberle AM; Mariani J; Eckhaus M; Herrup K; Bailly Y; Wynshaw-Boris A. 2000. ATM is a cytoplasmic protein in mouse brain required to prevent lysosomal accumulation. Proc Natl Acad Sci U S A 97(2):871-6. [PubMed: 10639172]  [MGI Ref ID J:59933]

Baulch JE; Li MW; Raabe OG. 2007. Effect of ATM heterozygosity on heritable DNA damage in mice following paternal F(0) germline irradiation. Mutat Res 616(1-2):34-45. [PubMed: 17161850]  [MGI Ref ID J:118241]

Bellani MA; Romanienko PJ; Cairatti DA; Camerini-Otero RD. 2005. SPO11 is required for sex-body formation, and Spo11 heterozygosity rescues the prophase arrest of Atm-/- spermatocytes. J Cell Sci 118(Pt 15):3233-45. [PubMed: 15998665]  [MGI Ref ID J:100203]

Bhandoola A; Dolnick B; Fayad N; Nussenzweig A; Singer A. 2000. Immature thymocytes undergoing receptor rearrangements are resistant to an Atm-dependent death pathway activated in mature T cells by double-stranded DNA breaks. J Exp Med 192(6):891-7. [PubMed: 10993919]  [MGI Ref ID J:112013]

Bishop AJ; Barlow C; Wynshaw-Boris AJ; Schiestl RH. 2000. Atm deficiency causes an increased frequency of intrachromosomal homologous recombination in mice. Cancer Res 60(2):395-9. [PubMed: 10667593]  [MGI Ref ID J:60230]

Bishop AJ; Hollander MC; Kosaras B; Sidman RL; Fornace AJ Jr; Schiestl RH. 2003. Atm-, p53-, and Gadd45a-deficient mice show an increased frequency of homologous recombination at different stages during development. Cancer Res 63(17):5335-43. [PubMed: 14500365]  [MGI Ref ID J:85514]

Bowen TJ; Yakushiji H; Montagna C; Jain S; Ried T; Wynshaw-Boris A. 2005. Atm heterozygosity cooperates with loss of Brca1 to increase the severity of mammary gland cancer and reduce ductal branching. Cancer Res 65(19):8736-46. [PubMed: 16204043]  [MGI Ref ID J:102687]

Cao L; Kim S; Xiao C; Wang RH; Coumoul X; Wang X; Li WM; Xu XL; De Soto JA; Takai H; Mai S; Elledge SJ; Motoyama N; Deng CX. 2006. ATM-Chk2-p53 activation prevents tumorigenesis at an expense of organ homeostasis upon Brca1 deficiency. EMBO J 25(10):2167-77. [PubMed: 16675955]  [MGI Ref ID J:108783]

Ch'ang HJ; Maj JG; Paris F; Xing HR; Zhang J; Truman JP; Cardon-Cardo C; Haimovitz-Friedman A; Kolesnick R; Fuks Z. 2005. ATM regulates target switching to escalating doses of radiation in the intestines. Nat Med 11(5):484-490. [PubMed: 15864314]  [MGI Ref ID J:98312]

Chiang JY; Jang IK; Hodes R; Gu H. 2007. Ablation of Cbl-b provides protection against transplanted and spontaneous tumors. J Clin Invest 117(4):1029-36. [PubMed: 17364027]  [MGI Ref ID J:121280]

Chiesa N; Barlow C; Wynshaw-Boris A; Strata P; Tempia F. 2000. Atm-deficient mice Purkinje cells show age-dependent defects in calcium spike bursts and calcium currents. Neuroscience 96(3):575-83. [PubMed: 10717437]  [MGI Ref ID J:61269]

Di Giacomo M; Barchi M; Baudat F; Edelmann W; Keeney S; Jasin M. 2005. Distinct DNA-damage-dependent and -independent responses drive the loss of oocytes in recombination-defective mouse mutants. Proc Natl Acad Sci U S A 102(3):737-42. [PubMed: 15640358]  [MGI Ref ID J:96250]

Eaton JS; Lin ZP; Sartorelli AC; Bonawitz ND; Shadel GS. 2007. Ataxia-telangiectasia mutated kinase regulates ribonucleotide reductase and mitochondrial homeostasis. J Clin Invest 117(9):2723-34. [PubMed: 17786248]  [MGI Ref ID J:127394]

Erker L; Schubert R; Elchuri S; Huang TT; Tarin D; Mueller K; Zielen S; Epstein CJ; Wynshaw-Boris A. 2006. Effect of the reduction of superoxide dismutase 1 and 2 or treatment with alpha-tocopherol on tumorigenesis in Atm-deficient mice. Free Radic Biol Med 41(4):590-600. [PubMed: 16863992]  [MGI Ref ID J:111281]

Erker L; Schubert R; Yakushiji H; Barlow C; Larson D; Mitchell JB; Wynshaw-Boris A. 2005. Cancer chemoprevention by the antioxidant tempol acts partially via the p53 tumor suppressor. Hum Mol Genet 14(12):1699-708. [PubMed: 15888486]  [MGI Ref ID J:101124]

Feldser D; Strong MA; Greider CW. 2006. Ataxia telangiectasia mutated (Atm) is not required for telomerase-mediated elongation of short telomeres. Proc Natl Acad Sci U S A 103(7):2249-51. [PubMed: 16467146]  [MGI Ref ID J:106070]

Freie BW; Ciccone SL; Li X; Plett PA; Orschell CM; Srour EF; Hanenberg H; Schindler D; Lee SH; Clapp DW. 2004. A role for the Fanconi anemia C protein in maintaining the DNA damage-induced G2 checkpoint. J Biol Chem 279(49):50986-93. [PubMed: 15377654]  [MGI Ref ID J:95193]

Gladdy RA; Nutter LM; Kunath T; Danska JS; Guidos CJ. 2006. p53-Independent apoptosis disrupts early organogenesis in embryos lacking both ataxia-telangiectasia mutated and Prkdc. Mol Cancer Res 4(5):311-8. [PubMed: 16687486]  [MGI Ref ID J:108789]

Gurley KE; Kemp CJ. 2001. Synthetic lethality between mutation in Atm and DNA-PK(cs) during murine embryogenesis. Curr Biol 11(3):191-4. [PubMed: 11231155]  [MGI Ref ID J:67533]

Hande MP; Balajee AS; Tchirkov A; Wynshaw-Boris A; Lansdorp PM. 2001. Extra-chromosomal telomeric DNA in cells from Atm(-/-) mice and patients with ataxia-telangiectasia. Hum Mol Genet 10(5):519-28. [PubMed: 11181576]  [MGI Ref ID J:67782]

Hishiya A; Ito M; Aburatani H; Motoyama N; Ikeda K; Watanabe K. 2005. Ataxia telangiectasia mutated (Atm) knockout mice as a model of osteopenia due to impaired bone formation. Bone 37(4):497-503. [PubMed: 16027059]  [MGI Ref ID J:102544]

Huang CY; Sharma GG; Walker LM; Bassing CH; Pandita TK; Sleckman BP. 2007. Defects in coding joint formation in vivo in developing ATM-deficient B and T lymphocytes. J Exp Med 204(6):1371-81. [PubMed: 17502661]  [MGI Ref ID J:125881]

Jack MT; Woo RA; Hirao A; Cheung A; Mak TW; Lee PW. 2002. Chk2 is dispensable for p53-mediated G1 arrest but is required for a latent p53-mediated apoptotic response. Proc Natl Acad Sci U S A 99(15):9825-9. [PubMed: 12097646]  [MGI Ref ID J:126186]

Karabinis ME; Larson D; Barlow C; Wynshaw-Boris A; Moser AR. 2001. Heterozygosity for a mutation in Brca1 or Atm does not increase susceptibility to ENU-induced mammary tumors in Apc(Min)/+ mice. Carcinogenesis 22(2):343-6. [PubMed: 11181458]  [MGI Ref ID J:67485]

Laposa RR; Henderson JT; Xu E; Wells PG. 2004. Atm-null mice exhibit enhanced radiation-induced birth defects and a hybrid form of embryonic programmed cell death indicating a teratological suppressor function for ATM. FASEB J 18(7):896-8. [PubMed: 15033931]  [MGI Ref ID J:118485]

Li B; Wang X; Rasheed N; Hu Y; Boast S; Ishii T; Nakayama K; Nakayama KI; Goff SP. 2004. Distinct roles of c-Abl and Atm in oxidative stress response are mediated by protein kinase C delta. Genes Dev 18(15):1824-37. [PubMed: 15289456]  [MGI Ref ID J:119329]

Liao MJ; Van Dyke T. 1999. Critical role for Atm in suppressing V(D)J recombination-driven thymic lymphoma. Genes Dev 13(10):1246-50. [PubMed: 10346813]  [MGI Ref ID J:55417]

Liao MJ; Yin C; Barlow C; Wynshaw-Boris A; van Dyke T. 1999. Atm is dispensable for p53 apoptosis and tumor suppression triggered by cell cycle dysfunction. Mol Cell Biol 19(4):3095-102. [PubMed: 10082576]  [MGI Ref ID J:53932]

Liu N; Stoica G; Yan M; Scofield VL; Qiang W; Lynn WS; Wong PK. 2005. ATM deficiency induces oxidative stress and endoplasmic reticulum stress in astrocytes Lab Invest 85(12):1471-80. [PubMed: 16189515]  [MGI Ref ID J:103477]

Liyanage M; Weaver Z; Barlow C; Coleman A; Pankratz DG; Anderson S; Wynshaw-Boris A; Ried T. 2000. Abnormal rearrangement within the alpha/delta T-cell receptor locus in lymphomas from atm-deficient mice Blood 96(5):1940-6. [PubMed: 10961898]  [MGI Ref ID J:64217]

Lumsden JM; McCarty T; Petiniot LK; Shen R; Barlow C; Wynn TA; Morse HC rd; Gearhart PJ; Wynshaw-Boris A; Max EE; Hodes RJ. 2004. Immunoglobulin class switch recombination is impaired in Atm-deficient mice. J Exp Med 200(9):1111-21. [PubMed: 15504820]  [MGI Ref ID J:94908]

Macleod MR; Ramage L; McGregor A; Seckl JR. 2003. Reduced NMDA-induced apoptosis in neurons lacking ataxia telangiectasia mutated protein. Neuroreport 14(2):215-7. [PubMed: 12598732]  [MGI Ref ID J:89866]

McConnell MJ; Kaushal D; Yang AH; Kingsbury MA; Rehen SK; Treuner K; Helton R; Annas EG; Chun J; Barlow C. 2004. Failed clearance of aneuploid embryonic neural progenitor cells leads to excess aneuploidy in the Atm-deficient but not the Trp53-deficient adult cerebral cortex. J Neurosci 24(37):8090-6. [PubMed: 15371510]  [MGI Ref ID J:109775]

Menisser-de Murcia J; Mark M; Wendling O; Wynshaw-Boris A; de Murcia G. 2001. Early embryonic lethality in PARP-1 Atm double-mutant mice suggests a functional synergy in cell proliferation during development. Mol Cell Biol 21(5):1828-32. [PubMed: 11238919]  [MGI Ref ID J:67341]

Miles PD; Treuner K; Latronica M; Olefsky JM; Barlow C. 2007. Impaired insulin secretion in a mouse model of ataxia telangiectasia. Am J Physiol Endocrinol Metab 293(1):E70-4. [PubMed: 17356010]  [MGI Ref ID J:122699]

Moens PB; Tarsounas M; Morita T; Habu T; Rottinghaus ST; Freire R; Jackson SP; Barlow C; Wynshaw-Boris A. 1999. The association of ATR protein with mouse meiotic chromosome cores. Chromosoma 108(2):95-102. [PubMed: 10382071]  [MGI Ref ID J:55411]

Morales M; Liu Y; Laiakis EC; Morgan WF; Nimer SD; Petrini JH. 2008. DNA damage signaling in hematopoietic cells: a role for Mre11 complex repair of topoisomerase lesions. Cancer Res 68(7):2186-93. [PubMed: 18381424]  [MGI Ref ID J:133303]

Morales M; Theunissen JW; Kim CF; Kitagawa R; Kastan MB; Petrini JH. 2005. The Rad50S allele promotes ATM-dependent DNA damage responses and suppresses ATM deficiency: implications for the Mre11 complex as a DNA damage sensor. Genes Dev 19(24):3043-54. [PubMed: 16357220]  [MGI Ref ID J:103922]

Mount HT; Martel JC; Fluit P; Wu Y; Gallo-Hendrikx E; Cosi C; Marien MR. 2004. Progressive sensorimotor impairment is not associated with reduced dopamine and high energy phosphate donors in a model of ataxia-telangiectasia. J Neurochem 88(6):1449-54. [PubMed: 15009646]  [MGI Ref ID J:90404]

Naz RK; Rajesh C. 2005. Gene knockouts that cause female infertility: search for novel contraceptive targets Front Biosci 10:2447-2459. [PubMed: 15970507]  [MGI Ref ID J:103183]

Paulson QX; Pusapati RV; Hong S; Weaks RL; Conti CJ; Johnson DG. 2008. Transgenic expression of E2F3a causes DNA damage leading to ATM-dependent apoptosis. Oncogene 27(36):4954-61. [PubMed: 18469863]  [MGI Ref ID J:138672]

Petiniot LK; Weaver Z; Barlow C; Shen R; Eckhaus M; Steinberg SM; Ried T; Wynshaw-Boris A; Hodes RJ. 2000. Recombinase-activating gene (RAG) 2-mediated V(D)J recombination is not essential for tumorigenesis in Atm-deficient mice. Proc Natl Acad Sci U S A 97(12):6664-9. [PubMed: 10841564]  [MGI Ref ID J:62720]

Petiniot LK; Weaver Z; Vacchio M; Shen R; Wangsa D; Barlow C; Eckhaus M; Steinberg SM; Wynshaw-Boris A; Ried T; Hodes RJ. 2002. RAG-mediated V(D)J recombination is not essential for tumorigenesis in Atm-deficient mice. Mol Cell Biol 22(9):3174-7. [PubMed: 11940674]  [MGI Ref ID J:75737]

Pusapati RV; Rounbehler RJ; Hong S; Powers JT; Yan M; Kiguchi K; McArthur MJ; Wong PK; Johnson DG. 2006. ATM promotes apoptosis and suppresses tumorigenesis in response to Myc. Proc Natl Acad Sci U S A 103(5):1446-51. [PubMed: 16432227]  [MGI Ref ID J:105997]

Qi L; Strong MA; Karim BO; Armanios M; Huso DL; Greider CW. 2003. Short telomeres and ataxia-telangiectasia mutated deficiency cooperatively increase telomere dysfunction and suppress tumorigenesis. Cancer Res 63(23):8188-96. [PubMed: 14678974]  [MGI Ref ID J:87091]

Qi L; Strong MA; Karim BO; Huso DL; Greider CW. 2005. Telomere fusion to chromosome breaks reduces oncogenic translocations and tumour formation. Nat Cell Biol 7(7):706-11. [PubMed: 15965466]  [MGI Ref ID J:100156]

Ramiro AR; Jankovic M; Callen E; Difilippantonio S; Chen HT; McBride KM; Eisenreich TR; Chen J; Dickins RA; Lowe SW; Nussenzweig A; Nussenzweig MC. 2006. Role of genomic instability and p53 in AID-induced c-myc-Igh translocations. Nature 440(7080):105-9. [PubMed: 16400328]  [MGI Ref ID J:106450]

Rasheed N; Wang X; Niu QT; Yeh J; Li B. 2006. Atm-deficient mice: an osteoporosis model with defective osteoblast differentiation and increased osteoclastogenesis. Hum Mol Genet 15(12):1938-48. [PubMed: 16644862]  [MGI Ref ID J:112068]

Reimann M; Loddenkemper C; Rudolph C; Schildhauer I; Teichmann B; Stein H; Schlegelberger B; Dorken B; Schmitt CA. 2007. The Myc-evoked DNA damage response accounts for treatment resistance in primary lymphomas in vivo. Blood 110(8):2996-3004. [PubMed: 17562874]  [MGI Ref ID J:125810]

Reina-San-Martin B; Chen HT; Nussenzweig A; Nussenzweig MC. 2004. ATM is required for efficient recombination between immunoglobulin switch regions. J Exp Med 200(9):1103-10. [PubMed: 15520243]  [MGI Ref ID J:94913]

Reliene R; Fischer E; Schiestl RH. 2004. Effect of N-acetyl cysteine on oxidative DNA damage and the frequency of DNA deletions in atm-deficient mice. Cancer Res 64(15):5148-53. [PubMed: 15289318]  [MGI Ref ID J:91873]

Reliene R; Goad ME; Schiestl RH. 2006. Developmental cell death in the liver and newborn lethality of Ku86 deficient mice suppressed by antioxidant N-acetyl-cysteine. DNA Repair (Amst) 5(11):1392-7. [PubMed: 16916625]  [MGI Ref ID J:115982]

Schubert R; Erker L; Barlow C; Yakushiji H; Larson D; Russo A; Mitchell JB; Wynshaw-Boris A. 2004. Cancer chemoprevention by the antioxidant tempol in Atm-deficient mice. Hum Mol Genet 13(16):1793-802. [PubMed: 15213104]  [MGI Ref ID J:91634]

Shackelford RE; Manuszak RP; Johnson CD; Hellrung DJ; Link CJ; Wang S. 2004. Iron chelators increase the resistance of Ataxia telangeictasia cells to oxidative stress. DNA Repair (Amst) 3(10):1263-72. [PubMed: 15336622]  [MGI Ref ID J:92530]

Shima N; Munroe RJ; Schimenti JC. 2004. The Mouse Genomic Instability Mutation chaos1 Is an Allele of Polq That Exhibits Genetic Interaction with Atm. Mol Cell Biol 24(23):10381-9. [PubMed: 15542845]  [MGI Ref ID J:94088]

Shreeram S; Hee WK; Demidov ON; Kek C; Yamaguchi H; Fornace AJ Jr; Anderson CW; Appella E; Bulavin DV. 2006. Regulation of ATM/p53-dependent suppression of myc-induced lymphomas by Wip1 phosphatase. J Exp Med 203(13):2793-9. [PubMed: 17158963]  [MGI Ref ID J:120284]

Stern N; Hochman A; Zemach N; Weizman N; Hammel I; Shiloh Y; Rotman G; Barzilai A. 2002. Accumulation of DNA damage and reduced levels of nicotine adenine dinucleotide in the brains of Atm-deficient mice. J Biol Chem 277(1):602-8. [PubMed: 11679583]  [MGI Ref ID J:73636]

Stracker TH; Couto SS; Cordon-Cardo C; Matos T; Petrini JH. 2008. Chk2 suppresses the oncogenic potential of DNA replication-associated DNA damage. Mol Cell 31(1):21-32. [PubMed: 18614044]  [MGI Ref ID J:138550]

Stracker TH; Morales M; Couto SS; Hussein H; Petrini JH. 2007. The carboxy terminus of NBS1 is required for induction of apoptosis by the MRE11 complex. Nature 447(7141):218-21. [PubMed: 17429352]  [MGI Ref ID J:129762]

Treuner K; Helton R; Barlow C. 2004. Loss of Rad52 partially rescues tumorigenesis and T-cell maturation in Atm-deficient mice. Oncogene 23(27):4655-61. [PubMed: 15122331]  [MGI Ref ID J:90941]

Turker MS; Gage BM; Rose JA; Ponomareva ON; Tischfield JA; Stambrook PJ; Barlow C; Wynshaw-Boris A. 1999. Solid tissues removed from ATM homozygous deficient mice do not exhibit a mutator phenotype for second-step autosomal mutations. Cancer Res 59(19):4781-3. [PubMed: 10519383]  [MGI Ref ID J:57980]

Umesako S; Fujisawa K; Iiga S; Mori N; Takahashi M; Hong DP; Song CW; Haga S; Imai S; Niwa O; Okumoto M. 2005. Atm heterozygous deficiency enhances development of mammary carcinomas in p53 heterozygous knockout mice. Breast Cancer Res 7(1):R164-70. [PubMed: 15642165]  [MGI Ref ID J:96285]

Umesako S; Iiga S; Takahashi M; Imura K; Mori N; Hong DP; Song CW; Niwa O; Okumoto M. 2007. Distinct pattern of allelic loss and inactivation of cadherin 1 and 5 genes in mammary carcinomas arising in p53(+/-) mice. J Radiat Res (Tokyo) 48(2):143-52. [PubMed: 17327688]  [MGI Ref ID J:122711]

Vacchio MS; Olaru A; Livak F; Hodes RJ. 2007. ATM deficiency impairs thymocyte maturation because of defective resolution of T cell receptor {alpha} locus coding end breaks. Proc Natl Acad Sci U S A 104(15):6323-8. [PubMed: 17405860]  [MGI Ref ID J:120845]

Wang S; Guo M; Ouyang H; Li X; Cordon-Cardo C; Kurimasa A; Chen DJ; Fuks Z; Ling CC; Li GC. 2000. The catalytic subunit of DNA-dependent protein kinase selectively regulates p53-dependent apoptosis but not cell-cycle arrest. Proc Natl Acad Sci U S A 97(4):1584-8. [PubMed: 10677503]  [MGI Ref ID J:126920]

Weil MM; Kittrell FS; Yu Y; McCarthy M; Zabriskie RC; Ullrich RL. 2001. Radiation induces genomic instability and mammary ductal dysplasia in Atm heterozygous mice. Oncogene 20(32):4409-11. [PubMed: 11466622]  [MGI Ref ID J:70611]

Williams BR; Mirzoeva OK; Morgan WF; Lin J; Dunnick W; Petrini JH. 2002. A murine model of nijmegen breakage syndrome. Curr Biol 12(8):648-53. [PubMed: 11967151]  [MGI Ref ID J:75956]

Winrow CJ; Pankratz DG; Vibat CR; Bowen TJ; Callahan MA; Warren AJ; Hilbush BS; Wynshaw-Boris A; Hasel KW; Weaver Z; Lockhart DJ; Barlow C. 2005. Aberrant recombination involving the granzyme locus occurs in Atm-/- T-cell lymphomas. Hum Mol Genet 14(18):2671-84. [PubMed: 16087685]  [MGI Ref ID J:102105]

Wu D; Yang H; Xiang W; Zhou L; Shi M; Julies G; Laplante JM; Ballard BR; Guo Z. 2005. Heterozygous mutation of ataxia-telangiectasia mutated gene aggravates hypercholesterolemia in apoE-deficient mice. J Lipid Res 46(7):1380-7. [PubMed: 15863839]  [MGI Ref ID J:100500]

Yan M; Kuang X; Qiang W; Shen J; Claypool K; Lynn WS; Wong PK. 2002. Prevention of thymic lymphoma development in atm-/- mice by dexamethasone. Cancer Res 62(18):5153-7. [PubMed: 12234978]  [MGI Ref ID J:79018]

Yan M; Kuang X; Scofield VL; Shen J; Lynn WS; Wong PK. 2007. The glucocorticoid receptor is increased in Atm-/- thymocytes and in Atm-/- thymic lymphoma cells, and its nuclear translocation counteracts c-myc expression. Steroids 72(5):415-21. [PubMed: 17418878]  [MGI Ref ID J:124565]

Yan M; Shen J; Person MD; Kuang X; Lynn WS; Atlas D; Wong PK. 2008. Endoplasmic reticulum stress and unfolded protein response in Atm-deficient thymocytes and thymic lymphoma cells are attributable to oxidative stress. Neoplasia 10(2):160-7. [PubMed: 18283338]  [MGI Ref ID J:136014]

Yan M; Zhu C; Liu N; Jiang Y; Scofield VL; Riggs PK; Qiang W; Lynn WS; Wong PK. 2006. ATM controls c-Myc and DNA synthesis during postnatal thymocyte development through regulation of redox state. Free Radic Biol Med 41(4):640-8. [PubMed: 16863997]  [MGI Ref ID J:111274]

Zenvirth D; Richler C; Bardhan A; Baudat F; Barzilai A; Wahrman J; Simchen G. 2003. Mammalian meiosis involves DNA double-strand breaks with 3' overhangs. Chromosoma 111(6):369-76. [PubMed: 12644952]  [MGI Ref ID J:83201]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX11

Colony Maintenance

Mating System	Heterozygote x Heterozygote         (Female x Male)
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 ~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 48 hours of 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
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.

General Terms and Conditions

See Terms of Use

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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Ordering and Purchasing Information

      Purchasing Information
      JAX^® Mice Orders
      Surgical Services

Contact Information
Orders & Technical Support
Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
Technical Support Email Form

Terms of Use

Terms of Use

General Terms and Conditions

OncoMouse^® requires a license from DuPont, see Licenses for Strains with OncoMouse^® Technology.

Contact information

General inquiries

Contracts Administration

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

JAX^® Mice & Services Conditions of Use

“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’s prior written authorization.”

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of MICE, products or services, The Jackson Laboratory will, at its option, provide credit or replacement for the MICE or product received or the services provided.

No Liability

In no event shall The Jackson Laboratory, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, products or services, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of The Jackson Laboratory, its agents or employees. In purchasing or receiving MICE, products or services from The Jackson Laboratory, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges The Jackson Laboratory from all such causes of action or damages, and further agrees to defend and indemnify The Jackson Laboratory from any costs or damages arising out of any third party claims.

MICE and biological materials are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

The foregoing represents the General Terms and Conditions applicable to The Jackson Laboratory’s MICE, products and services. In addition, special terms and conditions of sale of certain MICE, products and services may be set forth separately in The Jackson Laboratory web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, products and services by The Jackson Laboratory, and by its licensees and distributors.

Acceptance of delivery of MICE, products or services shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on The Jackson Laboratory, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, products services by The Jackson Laboratory.