Abstract
Apoptosis, a mechanism for removal of genetically damaged cells and for maintenance of desired size of cell populations, has been implicated in tumor development. Previously, we defined polymorphic loci for susceptibility to apoptosis of thymocytes Rapop1, Rapop2, and Rapop3 on mouse Chromosomes 16, 9, and 3, respectively, using recombinant congenic CcS/Dem strains, each of which contains a random set of 12.5% STS/A genome in the genetic background of BALB/cHeA. The STS/A alleles at these loci confer lower susceptibility to radiation-induced apoptosis of thymocytes than the BALB/cHeA. In the present study, we tested susceptibility of colon crypt cells to radiationinduced apoptosis. In contrast to apoptosis in thymus, the STS/A mice were more susceptible to apoptosis in colon than the BALB/ cHeA. Among the CcS/Dem strains, CcS-4, CcS-7, and CcS-16 were more susceptible to apoptosis in colon than the BALB/cHeA; in thymus, the CcS-7 mice are less susceptible, and the CcS-4 and CcS-16 are not different from the BALB/cHeA. Thus, individual CcS/Dem strains showed different apoptosis susceptibility in the two organs. Analysis of (CcS-7 × BALB/cHeA)F2 hybrids revealed linkage of susceptibility to radiation-induced apoptosis of colon crypt cells to two loci on Chrs 9 and 16, to which Rapop2 and Rapop1 are mapped. The STS/A allele at the locus on chromosome 9 results in high susceptibility to apoptosis of colon crypt cells in mice homozygous for the BALB/cHeA allele at the locus on Chr 16. Although these two loci may be identical to Rapop1 and Rapop2, they affect apoptosis in colon in a way different from that in thymus.
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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, 159–171
Bosma MJ, Carroll AM (1991) The SCID mouse mutant: definition, characterization, and potential uses. Annu Rev Immunol 9, 323–350
Craig, RH, Jabs EW, Zhou P, Kozopas KM, Hawkins AL, Rochelle JM, Seldin MF, Griffin CA (1994) Human and mouse chromosomal mapping of the myeloid cell leukemia-1 gene: MCL1 maps to human chromosome 1q21, a region that is frequently altered in preneoplastic and neoplastic disease. Genomics 23, 457–463
Danska JS, Pflumio F, Williams CJ, Huner O, Dick JE, Guidos CJ (1994) Rescue of T cell-specific V(D)J recombination in SCID mice by DNA damaging agents. Science 266, 405–455
Dietrich W, Katz H, Lincoln SE, Shin H-S, Friedman J, Dracopoli NC, Lander ES (1992) A genetic map of the mouse suitable for typing interspecific crosses. Genetics 131, 423–447
Dietrich WF, Miller J, Steen R, Merchant MA, Damron-Boles D, Husain Z, Dredge R, Daly MJ, Ingalls KA, O’Connor TJ, Evans CA, DeAngelis MM, Levinson DM, Kruglyyak L, Goodman N, Copeland NG, Jenkins NA, Hawkins TL, Stein L, Page DC, Lander ES (1996) A comprehensive genetic map of the mouse genome. Nature 380, 150–152
Gabrieli Y, Sherman Y, Ben-Sasson SA (1992) Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation. J Cell Biol 119, 493–501
Gatti RA (1991) Localizing the genes for ataxia-telangiectasia: a human model for inherited cancer susceptibility. Adv Cancer Res 56, 77–104
Groot PC, Moen CJA, Dietrich W, Stoye JP, Lander ES, Demant P (1992) The recombinant congenic strains for analysis of multigenic traits: genetic composition. FASEB J 6, 2826–2835
Ijiri K, Potten CS (1983) Response of intestinal cells of differing topographical and hierarchical status to ten cytotoxic drugs and five sources of radiation. Br J Cancer 47, 175–185
Kerr JFR, Wyllie AH, Currie AR (1972) Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 26, 239–257
Kisielow P, von Boehmer H (1995) Development and selection of T cells: facts and puzzles. Adv Immunol 58, 87–209
Laird PW, Zijderveld A, Linders K, Rudnicki MA, Jaenisch R, Berns A (1991) Simplified mammalian DNA isolation procedure. Nucleic Acids Res 19, 4293
Lander ES, Schork NJ (1994) Genetic dissection of complex traits. Science 265, 2037–2048
Matsuda Y, Imai T, Shiomi T, Saito T, Yamauchi M, Fukao T, Akao Y, Seki N, Ito H, Hori T (1996) Comparative genomic mapping of the ataxia-telangiectasia region in mouse, rat, and Syrian hamster. Genomics 34, 347–352
Merrit AJ, Potten CS, Watson AJM, Loh DY, Nakayama K, Nakayama K, Hickman JA (1995) Differential expression of bcl-2 in intestinal epithelia. Correlation with attenuation of apoptosis in colonic crypts and the incidence of colonic neoplasia. J Cell Sci 108, 2261–2271
Miller RD, Hogg J, Ozaki JH, Gell D, Jackson SP, Riblet R (1995) Gene for the catalytic subunit of mouse DNA-dependent protein kinase maps to the seid locus. Proc Natl Acad Sci USA 92, 10792–10795
Moen CJA, van der Valk MA, Snoek M, van Zutphen BFM, van Deimling O, Hart AAM, Demant P (1991) The recombinant congenic strains—a novel genetic tool applied to the study of colon tumor development in the mouse. Mamm Genome 1, 217–227
Moen CJA, Snoek M, Hart AAM, Demant P (1992) Scc-1, a novel colon cancer susceptibility gene in the mouse: linkage to CD44 (Ly-24, Pgp-1) on chromosome 2. Oncogene 7, 563–566
Moen CJA, Groot PC, Hart AAM, Snoek M, Demant P (1996) Fine mapping of colon tumor susceptibility (Scc) genes in the mouse, different from the genes known to be somatically mutated in colon cancer. Proc Natl Acad Sci USA 93, 1082–1086
Mori N, Okumoto M, Morimoto J, Imai S, Matsuyama T, Takamori Y, Yagasaki O (1992) Genetic analysis of susceptibility to radiationinduced apoptosis of thymocytes in mice. Int J Radiat Biol 62, 153–159
Mori N, Okumoto M, Hart AAM, Demant P (1995a) Apoptosis susceptibility genes on mouse chromosome 9 (Rapop2) and chromosome 3 (Rapop3). Genomics 30, 553–557
Mori N, Okumoto M, van der Valk M, Imai S, Haga S, Esaki K, Hart AAM, Demant P (1995b) Genetic dissection of susceptibility to radiation-induced apoptosis of thymocytes and mapping of Rapop1, a novel susceptibility gene. Genomics 25, 609–614
Murphy WJ, Durum SK, Anver MR, Ferris DK, McVicar DW, O’Shea JJ, Ruscetti SK, Smith MR, Young HA, Longo DL (1994) Induction of T cell differentiation and lymphomagenesis in the thymus of mice with severe combined immunodeficiency (SCID). J Immunol 153, 1004–1014
Potten CS (1992) The significance of spontaneous and induced apoptosis in the gastrointestinal tract of mice. Cancer Metastasis Rev 11, 179–195.
Sellins KS, Cohen JJ (1987) Gene induction by γ-irradiation leads to DNA fragmentation in lymphocytes. J Immunol 139, 3199–3206
Stassen APM, Groot PC, Eppig JT, Demant P (1996) Genetic composition of the recombinant congenic strains. Mamm Genome 7, 55–58
van Wezel T, Stassen APM, Moen CJA, Hart AAH, van der Valk MA, Demant P (1996) Interaction and single gene effects in colon tumor susceptibility in mice. Nat Genet 14, 468–470
Yamada T, Ohyama H (1988) Radiation-induced interphase death of rat thymocytes is internally programmed (apoptosis). Int J Radiat Biol 53, 65–75
Zhan Q, Biezczad CK, Bae I, Fornace Jr. AJ, Craig RW (1997) Induction of BCL2 family member MCL1 as an early response to DNA damage. Oncogene 14, 1031–1039
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Mori, N., van Wezel, T., van der Valk, M. et al. Genetics of susceptibility to radiation-induced apoptosis in colon: two loci on Chromosomes 9 and 16. Mammalian Genome 9, 377–380 (1998). https://doi.org/10.1007/s003359900773
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DOI: https://doi.org/10.1007/s003359900773