A novel mouse model for ataxia-telangiectasia with a N-terminal mutation displays a behavioral defect and a low incidence of lymphoma but no increased oxidative burden

Human Molecular Genetics

Volumn 24, Issue 22, 2015, Pages 6331-6349

  Campbell, Andrew ^a   Krupp, Brittany ^a   Bushman, Jared ^b   Noble, Mark ^a   Pröschel, Christoph ^a   Mayer Pröschel, Margot ^a  

^a UNIVERSITY OF ROCHESTER MEDICAL CENTER   (United States)

^b UNIVERSITY OF WYOMING SCHOOL OF PHARMACY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ATM PROTEIN; ATM PROTEIN, MOUSE; CELL CYCLE PROTEIN; DNA BINDING PROTEIN; TUMOR SUPPRESSOR PROTEIN;

ALTERNATIVE RNA SPLICING; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; ATAXIA TELANGIECTASIA; CELL PROLIFERATION; CEREBELLAR TISSUE; CEREBELLUM DEGENERATION; CONTROLLED STUDY; DNA DAMAGE; EXON; GENE MUTATION; GLUTAMATERGIC SYNAPSE; HIPPOCAMPAL NEURONAL CULTURE; IMMUNOPHENOTYPING; IONIZING RADIATION; LYMPHOMA; MITOCHONDRION; MOLECULAR GENETICS; MOUSE; NERVE ENDING; NONHUMAN; OXIDATIVE STRESS; PATHOGENESIS; PHENOTYPE; POST HOC ANALYSIS; PRIORITY JOURNAL; T CELL LYMPHOMA; WILD TYPE; ANIMAL; ANIMAL BEHAVIOR; C57BL MOUSE; DISEASE MODEL; ENZYMOLOGY; FEMALE; GENETIC ASSOCIATION STUDY; GENETICS; HUMAN; INCIDENCE; MALE; METABOLISM; MUTATION; OXIDATION REDUCTION REACTION; PHYSIOLOGY;

ANIMALS; ATAXIA TELANGIECTASIA; ATAXIA TELANGIECTASIA MUTATED PROTEINS; BEHAVIOR, ANIMAL; CELL CYCLE PROTEINS; DISEASE MODELS, ANIMAL; DNA DAMAGE; DNA-BINDING PROTEINS; FEMALE; GENETIC ASSOCIATION STUDIES; HUMANS; INCIDENCE; LYMPHOMA, T-CELL; MALE; MICE; MICE, INBRED C57BL; MUTATION; OXIDATION-REDUCTION; TUMOR SUPPRESSOR PROTEINS;

EID: 84949033551     PISSN: 09646906     EISSN: 14602083     Source Type: Journal    
DOI: 10.1093/hmg/ddv342     Document Type: Article

References (108)

1. Chun, H.H. and Gatti, R.A. (2004) Ataxia-telangiectasia, an evolving phenotype. DNA Repair (Amst), 3, 1187-1196.
2. Hecht, F. and McCaw, B.K. (1974) Letter: chromosomally marked lymphocyte clones in ataxia-telangiectasia. Lancet, 1, 563-564.
3. Gotoff, S.P., Amirmokri, E. and Liebner, E.J. (1967) Ataxia telangiectasia. Neoplasia, untoward response to x-irradiation, and tuberous sclerosis. Am. J. Dis. Child, 114, 617-625.
4. Taylor, A.M., Metcalfe, J.A., Oxford, J.M. and Harnden, D.G. (1976) Proceedings: The radiosensitivity at the chromosomal level of lymphocytes from patients with ataxia telangiectasia. Br. J. Radiol., 49, 561.
5. Peterson, R.D., Kelly, W.D. and Good, R.A. (1964) Ataxia-telangiectasia. Its association with a defective thymus, immunological-deficiency disease, and malignancy. Lancet, 1, 1189-1193.
6. Eisen, A.H., Karpati, G., Laszlo, T., Andermann, F., Robb, J.P. and Bacal, H.L. (1965) Immunologic deficiency in ataxia telangiectasia. N. Engl. J. Med., 272, 18-22.
7. Boder, E. and Sedgwick, R.P. (1958) Ataxia-telangiectasia; a familial syndrome of progressive cerebellar ataxia, oculocutaneous telangiectasia and frequent pulmonary infection. Pediatrics, 21, 526-554.
8. Savitsky, K., Sfez, S., Tagle, D.A., Ziv, Y., Sartiel, A., Collins, F. S., Shiloh, Y. and Rotman, G. (1995) The complete sequence of the coding region of the ATMgene reveals similarity to cell cycle regulators in different species. Hum. Mol. Genet., 4, 2025-2032.
9. Concannon, P. and Gatti, R.A. (1997) Diversity of ATM gene mutations detected in patients with ataxia-telangiectasia. Hum. Mutat., 10, 100-107.
10. Sandoval, N., Platzer, M., Rosenthal, A., Dork, T., Bendix, R., Skawran, B., Stuhrmann, M., Wegner, R.D., Sperling, K., Banin, S. et al. (1999) Characterization of ATM gene mutations in 66 ataxia telangiectasia families. Hum. Mol. Genet., 8, 69-79.
11. Li, A. and Swift, M. (2000) Mutations at the ataxia-telangiectasia locus and clinical phenotypes of A-T patients. Am. J. Med. Genet., 92, 170-177.
12. Taylor, A.M. and Byrd, P.J. (2005) Molecular pathology of ataxia telangiectasia. J. Clin. Pathol., 58, 1009-1015.
13. Verhagen, M.M., Last, J.I., Hogervorst, F.B., Smeets, D.F., Roeleveld, N., Verheijen, F., Catsman-Berrevoets, C.E., Wulffraat, N.M., Cobben, J.M., Hiel, J. et al. (2012) Presence of ATM protein and residual kinase activity correlates with the phenotype in ataxia-telangiectasia: a genotype-phenotype study. Hum. Mutat., 33, 561-571.
14. Morrell, D., Cromartie, E. and Swift, M. (1986) Mortality and cancer incidence in 263 patients with ataxia-telangiectasia. J. Natl. Cancer Inst., 77, 89-92.
15. Olsen, J.H., Hahnemann, J.M., Borresen-Dale, A.L., Brondum-Nielsen, K., Hammarstrom, L., Kleinerman, R., Kaariainen, H., Lonnqvist, T., Sankila, R., Seersholm, N. et al. (2001) Cancer in patients with ataxia-telangiectasia and in their relatives in the nordic countries. J. Natl. Cancer Inst., 93, 121-127.
16. Sandoval, C. and Swift, M. (1998) Treatment of lymphoid malignancies in patients with ataxia-telangiectasia. Med. Pediatr. Oncol., 31, 491-497.
17. Taylor, A.M., Metcalfe, J.A., Thick, J. and Mak, Y.F. (1996) Leukemia and lymphoma in ataxia telangiectasia. Blood, 87, 423-438.
18. Li, P., Goto, H., Kasahara, K., Matsuyama, M., Wang, Z., Yatabe, Y., Kiyono, T. and Inagaki, M. (2012) P90 RSK arranges Chk1 in the nucleus for monitoring of genomic integrity during cell proliferation. Mol. Biol. Cell, 23, 1582-1592.
19. Yang, Y. and Herrup, K. (2005) Loss of neuronal cell cycle control in ataxia-telangiectasia: a unified disease mechanism. J. Neurosci., 25, 2522-2529.
20. Daniel, J.A., Pellegrini, M., Lee, B.S., Guo, Z., Filsuf, D., Belkina, N.V., You, Z., Paull, T.T., Sleckman, B.P., Feigenbaum, L. et al. (2012) Loss of ATM kinase activity leads to embryonic lethality in mice. J Cell Biol., 198, 295-304.
21. Yamamoto, K., Wang, Y., Jiang, W., Liu, X., Dubois, R.L., Lin, C.S., Ludwig, T., Bakkenist, C.J. and Zha, S. (2012) Kinasedead ATM protein causes genomic instability and early embryonic lethality in mice. J. Cell Biol., 198, 305-313.
22. Lavin, M.F. (2013) The appropriateness of the mouse model for ataxia-telangiectasia: neurological defects but no neurodegeneration. DNA Repair (Amst), 12, 612-619.
23. Barlow, C., Hirotsune, S., Paylor, R., Liyanage, M., Eckhaus, M., Collins, F., Shiloh, Y., Crawley, J.N., Ried, T., Tagle, D. et al. (1996) Atm-deficient mice: a paradigm of ataxia telangiectasia. Cell, 86, 159-171.
24. Elson, A., Wang, Y., Daugherty, C.J., Morton, C.C., Zhou, F., Campos-Torres, J. and Leder, P. (1996) Pleiotropic defects in ataxia-telangiectasia protein-deficient mice. Proc. Natl. Acad. Sci. USA, 93, 13084-13089.
25. Borghesani, P.R., Alt, F.W., Bottaro, A., Davidson, L., Aksoy, S., Rathbun, G.A., Roberts, T.M., Swat,W., Segal, R.A. and Gu, Y. (2000) Abnormal development of Purkinje cells and lymphocytes in Atm mutant mice. Proc. Natl. Acad. Sci. USA, 97, 3336-3341.
26. Spring, K., Cross, S., Li, C., Watters, D., Ben-Senior, L., Waring, P., Ahangari, F., Lu, S.L., Chen, P., Misko, I. et al. (2001) Atm knock-in mice harboring an in-frame deletion corresponding to the human ATM 7636del9 common mutation exhibit a variant phenotype. Cancer Res., 61, 4561-4568.
27. Xu, Y. and Baltimore, D. (1996) Dual roles of ATM in the cellular response to radiation and in cell growth control. Genes Dev., 10, 2401-2410.
28. Herzog, K.H., Chong, M.J., Kapsetaki, M., Morgan, J.I. and McKinnon, P.J. (1998) Requirement for Atm in ionizing radiation-induced cell death in the developing central nervous system. Science, 280, 1089-1091.
29. Gilad, S., Bar-Shira, A., Harnik, R., Shkedy, D., Ziv, Y., Khosravi, R., Brown, K., Vanagaite, L., Xu, G., Frydman, M. et al. (1996) Ataxia-telangiectasia: founder effect among north African Jews. Hum. Mol. Genet., 5, 2033-2037.
30. Li, J., Chen, J., Vinters, H.V., Gatti, R.A. and Herrup, K. (2011) Stable brain ATM message and residual kinase-active ATM protein in ataxia-telangiectasia. J. Neurosci., 31, 7568-7577.
31. Ambrose, M., Goldstine, J.V. and Gatti, R.A. (2007) Intrinsic mitochondrial dysfunction in ATM-deficient lymphoblastoid cells. Hum. Mol. Genet., 16, 2154-2164.
32. Barlow, C., Dennery, P.A., Shigenaga, M.K., Smith, M.A., Morrow, J.D., Roberts, L.J., Wynshaw-Boris, A. and Levine, R. L. (1999) Loss of the ataxia-telangiectasia gene product causes oxidative damage in target organs. Proc. Natl. Acad. Sci. USA, 96, 9915-9919.
33. Barzilai, A., Rotman, G. and Shiloh, Y. (2002) ATM deficiency and oxidative stress: a new dimension of defective response to DNA damage. DNA Repair (Amst.), 1, 3-25.
34. Gilad, S., Khosravi, R., Shkedy, D., Uziel, T., Ziv, Y., Savitsky, K., Rotman, G., Smith, S., Chessa, L., Jorgensen, T.J. et al. (1996) Predominance of null mutations in ataxia-telangiectasia. Hum. Mol. Genet., 5, 433-439.
35. Xu, Y., Ashley, T., Brainerd, E.E., Bronson, R.T., Meyn, M.S. and Baltimore, D. (1996) Targeted disruption of ATM leads to growth retardation, chromosomal fragmentation during meiosis, immune defects, and thymic lymphoma. Genes Dev., 10, 2411-2422.
36. Shiloh, Y. and Becker, Y. (1982) Reduced inhibition of replicon initiation and chain elongation by neocarzinostatin in skin fibroblasts from patients with ataxia telangiectasia. Biochim. Biophys. Acta., 721, 485-488.
37. Paterson, M.C., Smith, B.P., Lohman, P.H., Anderson, A.K. and Fishman, L. (1976) Defective excision repair of gammaray-damaged DNA in human (ataxia telangiectasia) fibroblasts. Nature, 260, 444-447.
38. Shiloh, Y., Tabor, E. and Becker, Y. (1983) Abnormal response of ataxia-telangiectasia cells to agents that break the deoxyribose moiety of DNAvia a targeted free radical mechanism. Carcinogenesis, 4, 1317-1322.
39. Ross, W.E. and Bradley, M.O. (1981)DNA double-stranded breaks in mammalian cells after exposure to intercalating agents. Biochim. Biophys. Acta., 654, 129-134.
40. Tewey, K.M., Rowe, T.C., Yang, L., Halligan, B.D. and Liu, L.F. (1984) Adriamycin-induced DNA damage mediated by mammalian DNA topoisomerase II. Science, 226, 466-468.
41. Canman, C.E., Lim, D.S., Cimprich, K.A., Taya, Y., Tamai, K., Sakaguchi, K., Appella, E., Kastan, M.B. and Siliciano, J.D. (1998) Activation of the ATM kinase by ionizing radiation and phosphorylation of p53. Science, 281, 1677-1679.
42. Kastan, M.B., Zhan, Q., el-Deiry, W.S., Carrier, F., Jacks, T., Walsh, W.V., Plunkett, B.S., Vogelstein, B. and Fornace, A. J.(1992) A mammalian cell cycle checkpoint pathway utilizing p53 and GADD45 is defective in ataxia-telangiectasia. Cell, 71, 587-597.
43. Khosravi, R., Maya, R., Gottlieb, T., Oren, M., Shiloh, Y. and Shkedy, D. (1999) Rapid ATM-dependent phosphorylation of MDM2 precedes p53 accumulation in response to DNA damage. Proc. Natl. Acad. Sci. USA, 96, 14973-14977.
44. Das, K.C. and Dashnamoorthy, R. (2004) Hyperoxia activates the ATR-chk1 pathway and phosphorylates p53 at multiple sites. Am. J. Physiol. Lung Cell Mol. Physiol., 286, L87-L97.
45. Kim, W.J., Vo, Q.N., Shrivastav, M., Lataxes, T.A. and Brown, K.D. (2002) Aberrant methylation of the ATM promoter correlates with increased radiosensitivity in a human colorectal tumor cell line. Oncogene, 21, 3864-3871.
46. Chan, S.F., Sances, S., Brill, L.M., Okamoto, S., Zaidi, R., McKercher, S.R., Akhtar, M.W., Nakanishi, N. and Lipton, S. A. (2014) ATM-dependent phosphorylation of MEF2D promotes neuronal survival after DNA damage. J. Neurosci., 34, 4640-4653.
47. Biton, S., Dar, I., Mittelman, L., Pereg, Y., Barzilai, A. and Shiloh, Y. (2006) Nuclear ataxia-telangiectasia mutated (ATM) mediates the cellular response to DNA double strand breaks in human neuron-like cells. J. Biol. Chem., 281, 17482-17491.
48. McKinnon, P.J. (2012) ATM and the molecular pathogenesis of ataxia telangiectasia. Annu. Rev. Pathol., 7, 303-321.
49. Hollis, R.J., Kennaugh, A.A., Butterworth, S.V. and Taylor, A.M. (1987) Growth of large chromosomally abnormal T cell clones in ataxia telangiectasia patients is associated with translocation at 14q11. A model for other T cell neoplasia. Hum. Genet., 76, 389-395.
50. Heppell, A., Butterworth, S.V., Hollis, R.J., Kennaugh, A.A., Beatty, D.W. and Taylor, A.M. (1988) Breakage of the T cell receptor alpha chain locus in non malignant clones from patients with ataxia telangiectasia. Hum. Genet., 79, 360-364.
51. Russo, G., Isobe, M., Pegoraro, L., Finan, J., Nowell, P.C. and Croce, C.M. (1988) Molecular analysis of a t(7;14)(q35;q32) chromosome translocation in a T cell leukemia of a patient with ataxia telangiectasia. Cell, 53, 137-144.
52. Lipkowitz, S., Stern, M.H. and Kirsch, I.R. (1990) Hybrid T cell receptor genes formed by interlocus recombination in normal and ataxia-telangiectasis lymphocytes. J. Exp. Med., 172, 409-418.
53. Liyanage, M., Weaver, Z., Barlow, C., Coleman, A., Pankratz, D.G., Anderson, S., Wynshaw-Boris, A. and Ried, T. (2000) Abnormal rearrangement within the alpha/delta T-cell receptor locus in lymphomas from Atm-deficient mice. Blood, 96, 1940-1946.
54. Genik, P.C., Bielefeldt-Ohmann, H., Liu, X., Story, M.D., Ding, L., Bush, J.M., Fallgren, C.M. and Weil, M.M. (2014) Strain background determines lymphoma incidence in atm knockout mice. Neoplasia, 16, 129-136.
55. Hecht, F. and Hecht, B.K. (1990) Cancer in ataxia-telangiectasia patients. Cancer Genet. Cytogenet., 46, 9-19
56. Peterson, R.D., Cooper, M.D. and Good, R.A. (1966) Lymphoid tissue abnormalities associated with ataxia-telangiectasia. Am. J. Med., 41, 342-359.
57. Fiorilli, M., Businco, L., Pandolfi, F., Paganelli, R., Russo, G. and Aiuti, F. (1983) Heterogeneity of immunological abnormalities in ataxia-telangiectasia. J. Clin. Immunol., 3, 135-141.
58. Hathcock, K.S., Bowen, S., Livak, F. and Hodes, R.J. (2013) ATM influences the efficiency of TCRbeta rearrangement, subsequent TCRbeta-dependent T cell development, and generation of the pre-selection TCRbeta CDR3 repertoire. PLoS One, 8, e62188.
59. Bowen, S., Wangsa, D., Ried, T., Livak, F. and Hodes, R.J. (2013) Concurrent V(D)J recombination and DNA end instability increase interchromosomal trans-rearrangements in ATM-deficient thymocytes. Nucleic Acids Res., 41, 4535-4548.
60. Isoda, T., Takagi, M., Piao, J., Nakagama, S., Sato, M., Masuda, K., Ikawa, T., Azuma, M., Morio, T., Kawamoto, H. et al. (2012) Process for immune defect and chromosomal translocation during early thymocyte development lacking ATM. Blood, 120, 789-799.
61. Matei, I.R., Gladdy, R.A., Nutter, L.M., Canty, A., Guidos, C.J. and Danska, J.S. (2007) ATM deficiency disrupts Tcra locus integrity and the maturation of CD4+CD8+ thymocytes. Blood, 109, 1887-1896.
62. Westphal, C.H., Rowan, S., Schmaltz, C., Elson, A., Fisher, D. E. and Leder, P. (1997) atm and p53 cooperate in apoptosis and suppression of tumorigenesis, but not in resistance to acute radiation toxicity. Nat. Genet., 16, 397-401.
63. Gurley, K.E. and Kemp, C.J. (2007) Ataxia-telangiectasia mutated is not required for p53 induction and apoptosis in irradiated epithelial tissues. Mol. Cancer Res., 5, 1312-1318.
64. Callen, E., Jankovic, M.,Wong, N., Zha, S., Chen, H.T., Difilippantonio, S., Di Virgilio, M., Heidkamp, G., Alt, F.W., Nussenzweig, A. et al. (2009) Essential role for DNA-PKCS in DNA double-strand break repair and apoptosis in ATMdeficient lymphocytes. Mol. Cell, 34, 285-297.
65. Watters, D.J. (2003) Oxidative stress in ataxia telangiectasia. Redox Rep., 8, 23-29.
66. Valentin-Vega, Y.A., Maclean, K.H., Tait-Mulder, J., Milasta, S., Steeves, M., Dorsey, F.C., Cleveland, J.L., Green, D.R. and Kastan, M.B. (2012) Mitochondrial dysfunction in ataxia-telangiectasia. Blood, 119, 1490-1500.
67. Meredith, M.J. and Dodson, M.L. (1987) Impaired glutathione biosynthesis in cultured human ataxia-telangiectasia cells. Cancer Res., 47, 4576-4581.
68. Reichenbach, J., Schubert, R., Schindler, D., Muller, K., Bohles, H. and Zielen, S. (2002) Elevated oxidative stress in patients with ataxia telangiectasia. Antioxid. Redox Signal, 4, 465-469.
69. Reichenbach, J., Schubert, R., Schwan, C., Muller, K., Bohles, H.J. and Zielen, S. (1999) Anti-oxidative capacity in patients with ataxia telangiectasia. Clin. Exp. Immunol., 117, 535-539.
70. Kamsler, A., Daily, D., Hochman, A., Stern, N., Shiloh, Y., Rotman, G. and Barzilai, A. (2001) Increased oxidative stress in ataxia telangiectasia evidenced by alterations in redox state of brains from Atm-deficient mice. Cancer Res., 61, 1849-1854.
71. Quick, K.L. and Dugan, L.L. (2001) Superoxide stress identifies neurons at risk in a model of ataxia-telangiectasia. Ann. Neurol., 49, 627-635.
72. Ludwig, L.B., Valiati, V.H., Palazzo, R.P., Jardim, L.B., da Rosa, D.P., Bona, S., Rodrigues, G., Marroni, N.P., Pra, D. and Maluf, S.W. (2013) Chromosome instability and oxidative stress markers in patients with ataxia telangiectasia and their parents. Biomed. Res. Int., 2013, 762048.
73. Semlitsch, M., Shackelford, R.E., Zirkl, S., Sattler, W. and Malle, E. (2011) ATM protects against oxidative stress induced by oxidized low-density lipoprotein. DNA Repair (Amst.), 10, 848-860.
74. Eaton, J.S., Lin, Z.P., Sartorelli, A.C., Bonawitz, N.D. and Shadel, G.S. (2007) Ataxia-telangiectasia mutated kinase regulates ribonucleotide reductase and mitochondrial homeostasis. J. Clin. Invest., 117, 2723-2734.
75. Alexander, A., Cai, S.L., Kim, J., Nanez, A., Sahin, M., Mac-Lean, K.H., Inoki, K., Guan, K.L., Shen, J., Person, M.D. et al. (2010) ATM signals to TSC2 in the cytoplasm to regulate MTORC1 in response to ROS. Proc. Natl. Acad. Sci. USA, 107, 4153-4158.
76. Cosentino, C., Grieco, D. and Costanzo, V. (2011) ATM activates the pentose phosphate pathway promoting antioxidant defence and DNA repair. EMBO J., 30, 546-555.
77. Finkel, T. (2011) Signal transduction by reactive oxygen species. J. Cell Biol., 194, 7-15.
78. Weyemi, U., Redon, C.E., Aziz, T., Choudhuri, R., Maeda, D., Parekh, P.R., Bonner, M.Y., Arbiser, J.L. and Bonner, W.M. (2015) NADPH oxidase 4 is a critical mediator in Ataxia telangiectasia disease. Proc. Natl. Acad. Sci. USA, 112, 2121-2126.
79. Carlessi, L., Fusar Poli, E., Bechi, G., Mantegazza, M., Pascucci, B., Narciso, L., Dogliotti, E., Sala, C., Verpelli, C., Lecis, D. et al. (2014) Functional and molecular defects of HIPSC-derived neurons from patients with ATM deficiency. Cell Death Dis., 5, e1342.
80. El-Husseini, A.E., Schnell, E., Chetkovich, D.M., Nicoll, R.A. and Bredt, D.S. (2000) PSD-95 involvement in maturation of excitatory synapses. Science, 290, 1364-1368.
81. Watters, D., Kedar, P., Spring, K., Bjorkman, J., Chen, P., Gatei, M., Birrell, G., Garrone, B., Srinivasa, P., Crane, D.I. et al. (1999) Localization of a portion of extranuclear ATM to peroxisomes. J. Biol. Chem., 274, 34277-34282.
82. Zha, S., Guo, C., Boboila, C., Oksenych, V., Cheng, H.L., Zhang, Y.,Wesemann, D.R., Yuen, G., Patel, H., Goff, P.H. et al. (2011) ATMdamage response and XLF repair factor are functionally redundant in joining DNA breaks. Nature, 469, 250-254.
83. You, Z., Chahwan, C., Bailis, J., Hunter, T. and Russell, P. (2005) ATM activation and its recruitment to damaged DNA require binding to the C terminus of Nbs1. Mol. Cell Biol., 25, 5363-5379.
84. Lavin, M.F., Scott, S., Gueven, N., Kozlov, S., Peng, C. and Chen, P. (2004) Functional consequences of sequence alterations in the ATM gene. DNA Repair (Amst.), 3, 1197-1205.
85. McConville, C.M., Stankovic, T., Byrd, P.J., McGuire, G.M., Yao, Q.Y., Lennox, G.G. and Taylor, M.R. (1996) Mutations associated with variant phenotypes in ataxia-telangiectasia. Am. J. Hum. Genet., 59, 320-330.
86. Gilad, S., Chessa, L., Khosravi, R., Russell, P., Galanty, Y., Piane, M., Gatti, R.A., Jorgensen, T.J., Shiloh, Y. and Bar-Shira, A. (1998) Genotype-phenotype relationships in ataxiatelangiectasia and variants. Am. J. Hum. Genet., 62, 551-561.
87. Gilad, S., Khosravi, R., Harnik, R., Ziv, Y., Shkedy, D., Galanty, Y., Frydman, M., Levi, J., Sanal, O., Chessa, L. et al. (1998) Identification of ATM mutations using extended RT-PCR and restriction endonuclease fingerprinting, and elucidation of the repertoire of A-T mutations in Israel. Hum. Mutat., 11, 69-75.
88. Du, L., Pollard, J.M. and Gatti, R.A. (2007) Correction of prototypic ATM splicing mutations and aberrant ATM function with antisense morpholino oligonucleotides. Proc. Natl. Acad. Sci. USA, 104, 6007-6012.
89. Teraoka, S.N., Telatar, M., Becker-Catania, S., Liang, T., Onengut, S., Tolun, A., Chessa, L., Sanal, O., Bernatowska, E., Gatti, R.A. et al. (1999) Splicing defects in the ataxia-telangiectasia gene, ATM: underlying mutations and consequences. Am. J. Hum. Genet., 64, 1617-1631.
90. Lempiainen, H. and Halazonetis, T.D. (2009) Emerging common themes in regulation of PIKKs and PI3Ks. EMBO J., 28, 3067-3073.
91. Reuter, S., Gupta, S.C., Chaturvedi, M.M. and Aggarwal, B.B. (2010) Oxidative stress, inflammation, and cancer: how are they linked? Free Radic. Biol. Med., 49, 1603-1616.
92. Cremona, C.A. and Behrens, A. (2013) ATM signalling and cancer. Oncogene, 33, 3351-3360.
93. Verschoor, M.L., Ungard, R., Harbottle, A., Jakupciak, J.P., Parr, R.L. and Singh, G. (2013) Mitochondria and cancer: past, present, and future. Biomed. Res. Int., 2013, 612369.
94. Lightfoot, T.J., Skibola, C.F., Smith, A.G., Forrest, M.S., Adamson, P.J., Morgan, G.J., Bracci, P.M., Roman, E., Smith, M.T. and Holly, E.A. (2006) Polymorphisms in the oxidative stress genes, superoxide dismutase, glutathione peroxidase and catalase and risk of non-Hodgkin's lymphoma. Haematologica, 91, 1222-1227.
95. Kastan, M.B. (2007) Our cells get stressed too! Implications for human disease. Blood Cells Mol. Dis., 39, 148-150.
96. Reliene, R., Fleming, S.M., Chesselet, M.F. and Schiestl, R.H. (2008) Effects of antioxidants on cancer prevention and neuromotor performance in Atm deficient mice. Food Chem. Toxicol., 46, 1371-1377.
97. Schubert, R., Erker, L., Barlow, C., Yakushiji, H., Larson, D., Russo, A., Mitchell, J.B. and Wynshaw-Boris, A. (2004) Cancer chemoprevention by the antioxidant tempol in Atmdeficient mice. Hum. Mol. Genet., 13, 1793-1802.
98. Degan, P., d'Ischia, M., Pallardo, F.V., Zatterale, A., Brusco, A., Calzone, R., Cavalieri, S., Kavakli, K., Lloret, A., Manini, P. et al. (2007) Glutathione levels in blood from ataxia telangiectasia patients suggest in vivo adaptive mechanisms to oxidative stress. Clin. Biochem., 40, 666-670.
99. Kim, E., Niethammer, M., Rothschild, A., Jan, Y.N. and Sheng, M. (1995) Clustering of Shaker-type K+ channels by interaction with a family of membrane-associated guanylate kinases. Nature, 378, 85-88.
100. Hunt, C.A., Schenker, L.J. and Kennedy, M.B. (1996) PSD-95 is associated with the postsynaptic density and not with the presynaptic membrane at forebrain synapses. J. Neurosci., 16, 1380-1388.
101. Wahlsten, D., Rustay, N.R., Metten, P. and Crabbe, J.C. (2003) In search of a better mouse test. Trends Neurosci., 26, 132-136.
102. Trommsdorff, M., Gotthardt, M., Hiesberger, T., Shelton, J., Stockinger, W., Nimpf, J., Hammer, R.E., Richardson, J.A. and Herz, J. (1999) Reeler/Disabled-like disruption of neuronal migration in knockout mice lacking the VLDL receptor and ApoE receptor 2. Cell, 97, 689-701.
103. Zanni, G. and Bertini, E.S. (2011) X-linked disorders with cerebellar dysgenesis. Orphanet. J. Rare Dis., 6, 24.
104. Yang, Y., Hui, C.W., Li, J. and Herrup, K. (2014) The interaction of the atm genotype with inflammation and oxidative stress. PLOS One, 9, e85863.
105. Hoch, R.V. and Soriano, P. (2006) Context-specific requirements for Fgfr1 signaling through Frs2 and Frs3 during mouse development. Development, 133, 663-673.
106. Robinson, J.T., Thorvaldsdottir, H., Winckler, W., Guttman, M., Lander, E.S., Getz, G. and Mesirov, J.P. (2011) Integrative genomics viewer. Nat. Biotechnol., 29, 24-26.
107. Thorvaldsdottir, H., Robinson, J.T. and Mesirov, J.P. (2013) Integrative Genomics Viewer (IGV): high-performance genomics data visualization and exploration. Brief Bioinform., 14, 178-192.
108. Schneider, C.A., Rasband, W.S. and Eliceiri, K.W. (2012) NIH Image to Image J: 25 years of image analysis. Nat. Methods, 9, 671-675.