Abstract
The transgenic mice were produced by injecting eggs of B6 and C3H/HeJ mice with the human E mu-myc gene. Preferential development of B lymphomas was observed in the B6 transgenic mice, whereas the C3H/HeJ transgenic mice developed mostly T lymphomas. The phenotypic activation of B lineage cells but not of T lineage cells was detected in the prelymphomatous transgenic mice of both strains. The transgene was similarly expressed in B and T cells of the transgenic mice of both strains. These results suggest that a high incidence of T lymphomas in the C3H/HeJ transgenic mice may not be due to the preferential activation of or the preferential E mu-myc expression in T lymphocytes. When the bone marrow or fetal liver cells from the prelymphomatous transgenic mice of both strains were transferred into irradiated normal C3H/HeJ mice, most of the recipients developed T lymphomas. Moreover, even when irradiated B6 mice received the hematopoietic stem cells from the prelymphomatous B6 transgenic mice, the incidence of T lymphoma increased up to 50%. These findings suggest that B6 and C3H/HeJ mice might provide the environment that supports the development or growth of B and T lymphomas, respectively, and that such an environment could be modified by irradiation of the mice.
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- Adams J. M., Harris A. W., Pinkert C. A., Corcoran L. M., Alexander W. S., Cory S., Palmiter R. D., Brinster R. L. The c-myc oncogene driven by immunoglobulin enhancers induces lymphoid malignancy in transgenic mice. Nature. 1985 Dec 12;318(6046):533–538. doi: 10.1038/318533a0. [DOI] [PubMed] [Google Scholar]
- Alexander W. S., Schrader J. W., Adams J. M. Expression of the c-myc oncogene under control of an immunoglobulin enhancer in E mu-myc transgenic mice. Mol Cell Biol. 1987 Apr;7(4):1436–1444. doi: 10.1128/mcb.7.4.1436. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Alitalo K., Bishop J. M., Smith D. H., Chen E. Y., Colby W. W., Levinson A. D. Nucleotide sequence to the v-myc oncogene of avian retrovirus MC29. Proc Natl Acad Sci U S A. 1983 Jan;80(1):100–104. doi: 10.1073/pnas.80.1.100. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bernard O., Cory S., Gerondakis S., Webb E., Adams J. M. Sequence of the murine and human cellular myc oncogenes and two modes of myc transcription resulting from chromosome translocation in B lymphoid tumours. EMBO J. 1983;2(12):2375–2383. doi: 10.1002/j.1460-2075.1983.tb01749.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
- Dalla-Favera R., Bregni M., Erikson J., Patterson D., Gallo R. C., Croce C. M. Human c-myc onc gene is located on the region of chromosome 8 that is translocated in Burkitt lymphoma cells. Proc Natl Acad Sci U S A. 1982 Dec;79(24):7824–7827. doi: 10.1073/pnas.79.24.7824. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Darveau A., Pelletier J., Sonenberg N. Differential efficiencies of in vitro translation of mouse c-myc transcripts differing in the 5' untranslated region. Proc Natl Acad Sci U S A. 1985 Apr;82(8):2315–2319. doi: 10.1073/pnas.82.8.2315. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dunnick W., Shell B. E., Dery C. DNA sequences near the site of reciprocal recombination between a c-myc oncogene and an immunoglobulin switch region. Proc Natl Acad Sci U S A. 1983 Dec;80(23):7269–7273. doi: 10.1073/pnas.80.23.7269. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Early P., Huang H., Davis M., Calame K., Hood L. An immunoglobulin heavy chain variable region gene is generated from three segments of DNA: VH, D and JH. Cell. 1980 Apr;19(4):981–992. doi: 10.1016/0092-8674(80)90089-6. [DOI] [PubMed] [Google Scholar]
- Eick D., Piechaczyk M., Henglein B., Blanchard J. M., Traub B., Kofler E., Wiest S., Lenoir G. M., Bornkamm G. W. Aberrant c-myc RNAs of Burkitt's lymphoma cells have longer half-lives. EMBO J. 1985 Dec 30;4(13B):3717–3725. doi: 10.1002/j.1460-2075.1985.tb04140.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Erikson J., Miller D. A., Miller O. J., Abcarian P. W., Skurla R. M., Mushinski J. F., Croce C. M. The c-myc oncogene is translocated to the involved chromosome 12 in mouse plasmacytoma. Proc Natl Acad Sci U S A. 1985 Jun;82(12):4212–4216. doi: 10.1073/pnas.82.12.4212. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ford A. M., Watt S. M., Furley A. J., Molgaard H. V., Greaves M. F. Cell lineage specificity of chromatin configuration around the immunoglobulin heavy chain enhancer. EMBO J. 1988 Aug;7(8):2393–2399. doi: 10.1002/j.1460-2075.1988.tb03084.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fujita T., Ohno S., Yasumitsu H., Taniguchi T. Delimitation and properties of DNA sequences required for the regulated expression of human interferon-beta gene. Cell. 1985 Jun;41(2):489–496. doi: 10.1016/s0092-8674(85)80022-2. [DOI] [PubMed] [Google Scholar]
- Glode L. M., Rosenstreich D. L. Genetic control of B cell activation by bacterial lipopolysaccharide is mediated by multiple distinct genes or alleles. J Immunol. 1976 Dec;117(6):2061–2066. [PubMed] [Google Scholar]
- Grosschedl R., Baltimore D. Cell-type specificity of immunoglobulin gene expression is regulated by at least three DNA sequence elements. Cell. 1985 Jul;41(3):885–897. doi: 10.1016/s0092-8674(85)80069-6. [DOI] [PubMed] [Google Scholar]
- Grosschedl R., Weaver D., Baltimore D., Costantini F. Introduction of a mu immunoglobulin gene into the mouse germ line: specific expression in lymphoid cells and synthesis of functional antibody. Cell. 1984 Oct;38(3):647–658. doi: 10.1016/0092-8674(84)90259-9. [DOI] [PubMed] [Google Scholar]
- Hanahan D. Dissecting multistep tumorigenesis in transgenic mice. Annu Rev Genet. 1988;22:479–519. doi: 10.1146/annurev.ge.22.120188.002403. [DOI] [PubMed] [Google Scholar]
- Hayday A. C., Gillies S. D., Saito H., Wood C., Wiman K., Hayward W. S., Tonegawa S. Activation of a translocated human c-myc gene by an enhancer in the immunoglobulin heavy-chain locus. 1984 Jan 26-Feb 1Nature. 307(5949):334–340. doi: 10.1038/307334a0. [DOI] [PubMed] [Google Scholar]
- Hayward W. S., Neel B. G., Astrin S. M. Activation of a cellular onc gene by promoter insertion in ALV-induced lymphoid leukosis. Nature. 1981 Apr 9;290(5806):475–480. doi: 10.1038/290475a0. [DOI] [PubMed] [Google Scholar]
- KAPLAN H. S., BROWN M. B. Development of lymphoid tumors in nonirradiated thymic grafts in thymectomized irradiated mice. Science. 1954 Apr 2;119(3092):439–440. doi: 10.1126/science.119.3092.439. [DOI] [PubMed] [Google Scholar]
- KAPLAN H. S., CARNES W. H., BROWN M. B., HIRSCH B. B. Indirect induction of lymphomas in irradiated mice. I. Tumor incidence and morphology in mice bearing nonirradiated thymic grafts. Cancer Res. 1956 Jun;16(5):422–425. [PubMed] [Google Scholar]
- KAPLAN H. S., HIRSCH B. B., BROWN M. B. Indirect induction of lymphomas in irradiated mice. IV. Genetic evidence of the origin of the tumor cells from the thymic grafts. Cancer Res. 1956 Jun;16(5):434–436. [PubMed] [Google Scholar]
- Keath E. J., Kelekar A., Cole M. D. Transcriptional activation of the translocated c-myc oncogene in mouse plasmacytomas: similar RNA levels in tumor and proliferating normal cells. Cell. 1984 Jun;37(2):521–528. doi: 10.1016/0092-8674(84)90382-9. [DOI] [PubMed] [Google Scholar]
- Klinken S. P., Alexander W. S., Adams J. M. Hemopoietic lineage switch: v-raf oncogene converts Emu-myc transgenic B cells into macrophages. Cell. 1988 Jun 17;53(6):857–867. doi: 10.1016/s0092-8674(88)90309-1. [DOI] [PubMed] [Google Scholar]
- LIEBERMAN M., KAPLAN H. S. Leukemogenic activity of filtrates from radiation-induced lymphoid tumors of mice. Science. 1959 Aug 14;130(3372):387–388. doi: 10.1126/science.130.3372.387. [DOI] [PubMed] [Google Scholar]
- Langdon W. Y., Harris A. W., Cory S., Adams J. M. The c-myc oncogene perturbs B lymphocyte development in E-mu-myc transgenic mice. Cell. 1986 Oct 10;47(1):11–18. doi: 10.1016/0092-8674(86)90361-2. [DOI] [PubMed] [Google Scholar]
- Leder P., Battey J., Lenoir G., Moulding C., Murphy W., Potter H., Stewart T., Taub R. Translocations among antibody genes in human cancer. Science. 1983 Nov 18;222(4625):765–771. doi: 10.1126/science.6356357. [DOI] [PubMed] [Google Scholar]
- Lieberman M., Hansteen G. A., McCune J. M., Scott M. L., White J. H., Weissman I. L. Indirect induction of radiation lymphomas in mice. Evidence for a novel, transmissible leukemogen. J Exp Med. 1987 Dec 1;166(6):1883–1893. doi: 10.1084/jem.166.6.1883. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Marcu K. B., Harris L. J., Stanton L. W., Erikson J., Watt R., Croce C. M. Transcriptionally active c-myc oncogene is contained within NIARD, a DNA sequence associated with chromosome translocations in B-cell neoplasia. Proc Natl Acad Sci U S A. 1983 Jan;80(2):519–523. doi: 10.1073/pnas.80.2.519. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nakauchi H., Osada H., Yagita H., Okumura K. Molecular evidence that SJL reticulum cell sarcomas are derived from pre-B cell. Clonal rearrangement of heavy chain but not of light chain immunoglobulin genes. J Immunol. 1987 Oct 15;139(8):2803–2809. [PubMed] [Google Scholar]
- Naparstek E., FitzGerald T. J., Sakakeeny M. A., Klassen V., Pierce J. H., Woda B. A., Falco J., Fitzgerald S., Nizin P., Greenberger J. S. Induction of malignant transformation of cocultivated hematopoietic stem cells by X-irradiation of murine bone marrow stromal cells in vitro. Cancer Res. 1986 Sep;46(9):4677–4684. [PubMed] [Google Scholar]
- Nishikura K., ar-Rushdi A., Erikson J., Watt R., Rovera G., Croce C. M. Differential expression of the normal and of the translocated human c-myc oncogenes in B cells. Proc Natl Acad Sci U S A. 1983 Aug;80(15):4822–4826. doi: 10.1073/pnas.80.15.4822. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nussenzweig M. C., Schmidt E. V., Shaw A. C., Sinn E., Campos-Torres J., Mathey-Prevot B., Pattengale P. K., Leder P. A human immunoglobulin gene reduces the incidence of lymphomas in c-Myc-bearing transgenic mice. Nature. 1988 Dec 1;336(6198):446–450. doi: 10.1038/336446a0. [DOI] [PubMed] [Google Scholar]
- Piechaczyk M., Yang J. Q., Blanchard J. M., Jeanteur P., Marcu K. B. Posttranscriptional mechanisms are responsible for accumulation of truncated c-myc RNAs in murine plasma cell tumors. Cell. 1985 Sep;42(2):589–597. doi: 10.1016/0092-8674(85)90116-3. [DOI] [PubMed] [Google Scholar]
- Rabbitts P. H., Forster A., Stinson M. A., Rabbitts T. H. Truncation of exon 1 from the c-myc gene results in prolonged c-myc mRNa stability. EMBO J. 1985 Dec 30;4(13B):3727–3733. doi: 10.1002/j.1460-2075.1985.tb04141.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rabbitts T. H., Forster A., Hamlyn P., Baer R. Effect of somatic mutation within translocated c-myc genes in Burkitt's lymphoma. Nature. 1984 Jun 14;309(5969):592–597. doi: 10.1038/309592a0. [DOI] [PubMed] [Google Scholar]
- Saito H., Hayday A. C., Wiman K., Hayward W. S., Tonegawa S. Activation of the c-myc gene by translocation: a model for translational control. Proc Natl Acad Sci U S A. 1983 Dec;80(24):7476–7480. doi: 10.1073/pnas.80.24.7476. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sakano H., Hüppi K., Heinrich G., Tonegawa S. Sequences at the somatic recombination sites of immunoglobulin light-chain genes. Nature. 1979 Jul 26;280(5720):288–294. doi: 10.1038/280288a0. [DOI] [PubMed] [Google Scholar]
- Schmidt E. V., Pattengale P. K., Weir L., Leder P. Transgenic mice bearing the human c-myc gene activated by an immunoglobulin enhancer: a pre-B-cell lymphoma model. Proc Natl Acad Sci U S A. 1988 Aug;85(16):6047–6051. doi: 10.1073/pnas.85.16.6047. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schöler H. R., Gruss P. Cell type-specific transcriptional enhancement in vitro requires the presence of trans-acting factors. EMBO J. 1985 Nov;4(11):3005–3013. doi: 10.1002/j.1460-2075.1985.tb04036.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Siu G., Kronenberg M., Strauss E., Haars R., Mak T. W., Hood L. The structure, rearrangement and expression of D beta gene segments of the murine T-cell antigen receptor. 1984 Sep 27-Oct 3Nature. 311(5984):344–350. doi: 10.1038/311344a0. [DOI] [PubMed] [Google Scholar]
- Suda Y., Aizawa S., Hirai S., Inoue T., Furuta Y., Suzuki M., Hirohashi S., Ikawa Y. Driven by the same Ig enhancer and SV40 T promoter ras induced lung adenomatous tumors, myc induced pre-B cell lymphomas and SV40 large T gene a variety of tumors in transgenic mice. EMBO J. 1987 Dec 20;6(13):4055–4065. doi: 10.1002/j.1460-2075.1987.tb02751.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Van Doren K., Hanahan D., Gluzman Y. Infection of eucaryotic cells by helper-independent recombinant adenoviruses: early region 1 is not obligatory for integration of viral DNA. J Virol. 1984 May;50(2):606–614. doi: 10.1128/jvi.50.2.606-614.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Watson D. K., Reddy E. P., Duesberg P. H., Papas T. S. Nucleotide sequence analysis of the chicken c-myc gene reveals homologous and unique coding regions by comparison with the transforming gene of avian myelocytomatosis virus MC29, delta gag-myc. Proc Natl Acad Sci U S A. 1983 Apr;80(8):2146–2150. doi: 10.1073/pnas.80.8.2146. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Watson J., Kelly K., Largen M., Taylor B. A. The genetic mapping of a defective LPS response gene in C3H/HeJ mice. J Immunol. 1978 Feb;120(2):422–424. [PubMed] [Google Scholar]
- Westaway D., Payne G., Varmus H. E. Proviral deletions and oncogene base-substitutions in insertionally mutagenized c-myc alleles may contribute to the progression of avian bursal tumors. Proc Natl Acad Sci U S A. 1984 Feb;81(3):843–847. doi: 10.1073/pnas.81.3.843. [DOI] [PMC free article] [PubMed] [Google Scholar]
- van Lohuizen M., Verbeek S., Krimpenfort P., Domen J., Saris C., Radaszkiewicz T., Berns A. Predisposition to lymphomagenesis in pim-1 transgenic mice: cooperation with c-myc and N-myc in murine leukemia virus-induced tumors. Cell. 1989 Feb 24;56(4):673–682. doi: 10.1016/0092-8674(89)90589-8. [DOI] [PubMed] [Google Scholar]