Skip to main content
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1982 Dec;79(23):7425–7429. doi: 10.1073/pnas.79.23.7425

Mutant immunoglobulin genes have repetitive DNA elements inserted into their intervening sequences.

R G Hawley, M J Shulman, H Murialdo, D M Gibson, N Hozumi
PMCID: PMC347352  PMID: 6296832

Abstract

The kappa light chain genes from two mutant hybridoma cell lines defective in kappa light chain synthesis were isolated and compared to the wild-type kappa light chain gene. In each case, the mutant kappa light chain genes were found to contain repetitive DNA elements in their intervening sequences that were not present in the intervening sequences of the wild-type kappa light chain gene. These elements were found to be related to the genes of intracisternal A particles. These results suggest that the decreased production of kappa light chain in the mutant cell lines is due to the presence of the intracisternal A particle-related genes.

Full text

PDF
7425

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Becker A., Gold M. Isolation of the bacteriophage lambda A-gene protein. Proc Natl Acad Sci U S A. 1975 Feb;72(2):581–585. doi: 10.1073/pnas.72.2.581. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Benton W. D., Davis R. W. Screening lambdagt recombinant clones by hybridization to single plaques in situ. Science. 1977 Apr 8;196(4286):180–182. doi: 10.1126/science.322279. [DOI] [PubMed] [Google Scholar]
  3. Bernard O., Hozumi N., Tonegawa S. Sequences of mouse immunoglobulin light chain genes before and after somatic changes. Cell. 1978 Dec;15(4):1133–1144. doi: 10.1016/0092-8674(78)90041-7. [DOI] [PubMed] [Google Scholar]
  4. Bernards A., Van der Ploeg L. H., Frasch A. C., Borst P., Boothroyd J. C., Coleman S., Cross G. A. Activation of trypanosome surface glycoprotein genes involves a duplication-transposition leading to an altered 3' end. Cell. 1981 Dec;27(3 Pt 2):497–505. doi: 10.1016/0092-8674(81)90391-3. [DOI] [PubMed] [Google Scholar]
  5. Biczysko W., Pienkowski M., Solter D., Koprowski H. Virus particles in early mouse embryos. J Natl Cancer Inst. 1973 Sep;51(3):1041–1050. doi: 10.1093/jnci/51.3.1041. [DOI] [PubMed] [Google Scholar]
  6. Calarco P. G., Szollosi D. Intracisternal A particles in ova and preimplantation stages of the mouse. Nat New Biol. 1973 May 16;243(124):91–93. [PubMed] [Google Scholar]
  7. Chase D. G., Pikó L. Expression of A- and C-type particles in early mouse embryos. J Natl Cancer Inst. 1973 Dec;51(6):1971–1975. doi: 10.1093/jnci/51.6.1971. [DOI] [PubMed] [Google Scholar]
  8. Cole M. D., Ono M., Huang R. C. Intracisternal A-particle genes: structure of adjacent genes and mapping of the boundaries of the transcriptional unit. J Virol. 1982 Apr;42(1):123–130. doi: 10.1128/jvi.42.1.123-130.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. DALTON A. J., POTTER M., MERWIN R. M. Some ultrastructural characteristics of a series of primary and transplanted plasma-cell tumors of the mouse. J Natl Cancer Inst. 1961 May;26:1221–1267. [PubMed] [Google Scholar]
  10. Davis M. M., Calame K., Early P. W., Livant D. L., Joho R., Weissman I. L., Hood L. An immunoglobulin heavy-chain gene is formed by at least two recombinational events. Nature. 1980 Feb 21;283(5749):733–739. doi: 10.1038/283733a0. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. Hozumi N., Brack C., Pirrotta V., Lenhard-Schuller R., Tonegawa S. Characterization of a mouse DNA clone containing an immunoglobulin variable region gene. Nucleic Acids Res. 1978 Jun;5(6):1779–1799. doi: 10.1093/nar/5.6.1779. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hozumi N., Hawley R. G., Murialdo H. Molecular cloning of an immunoglobulin kappa constant gene from NZB mouse. Gene. 1981 Mar;13(2):163–172. doi: 10.1016/0378-1119(81)90005-6. [DOI] [PubMed] [Google Scholar]
  14. Hozumi N., Tonegawa S. Evidence for somatic rearrangement of immunoglobulin genes coding for variable and constant regions. Proc Natl Acad Sci U S A. 1976 Oct;73(10):3628–3632. doi: 10.1073/pnas.73.10.3628. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hozumi N., Wu G. E., Murialdo H., Roberts L., Vetter D., Fife W. L., Whiteley M., Sadowski P. RNA splicing mutation in an aberrantly rearranged immunoglobulin lambda I gene. Proc Natl Acad Sci U S A. 1981 Nov;78(11):7019–7023. doi: 10.1073/pnas.78.11.7019. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Jenkins N. A., Copeland N. G., Taylor B. A., Lee B. K. Dilute (d) coat colour mutation of DBA/2J mice is associated with the site of integration of an ecotropic MuLV genome. Nature. 1981 Oct 1;293(5831):370–374. doi: 10.1038/293370a0. [DOI] [PubMed] [Google Scholar]
  17. Kataoka T., Kawakami T., Takahashi N., Honjo T. Rearrangement of immunoglobulin gamma 1-chain gene and mechanism for heavy-chain class switch. Proc Natl Acad Sci U S A. 1980 Feb;77(2):919–923. doi: 10.1073/pnas.77.2.919. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kuff E. L., Smith L. A., Lueders K. K. Intracisternal A-particle genes in Mus musculus: a conserved family of retrovirus-like elements. Mol Cell Biol. 1981 Mar;1(3):216–227. doi: 10.1128/mcb.1.3.216. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Köhler G., Milstein C. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature. 1975 Aug 7;256(5517):495–497. doi: 10.1038/256495a0. [DOI] [PubMed] [Google Scholar]
  20. Lazure C., Hum W. T., Gibson D. M. Sequence diversity within a subgroup of mouse immunoglobulin kappa chains controlled by the IgK-Ef2 locus. J Exp Med. 1981 Jul 1;154(1):146–155. doi: 10.1084/jem.154.1.146. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Liu C. P., Tucker P. W., Mushinski J. F., Blattner F. R. Mapping of heavy chain genes for mouse immunoglobulins M and D. Science. 1980 Sep 19;209(4463):1348–1353. doi: 10.1126/science.6774414. [DOI] [PubMed] [Google Scholar]
  22. Lueders K. K., Kuff E. L. Intracisternal A-particle genes: identification in the genome of Mus musculus and comparison of multiple isolates from a mouse gene library. Proc Natl Acad Sci U S A. 1980 Jun;77(6):3571–3575. doi: 10.1073/pnas.77.6.3571. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Lueders K. K., Kuff E. L. Sequences associated with intracisternal A particles are reiterated in the mouse genome. Cell. 1977 Dec;12(4):963–972. doi: 10.1016/0092-8674(77)90161-1. [DOI] [PubMed] [Google Scholar]
  24. Lueders K., Leder A., Leder P., Kuff E. Association between a transposed alpha-globin pseudogene and retrovirus-like elements in the BALB/c mouse genome. Nature. 1982 Feb 4;295(5848):426–428. doi: 10.1038/295426a0. [DOI] [PubMed] [Google Scholar]
  25. Maniatis T., Hardison R. C., Lacy E., Lauer J., O'Connell C., Quon D., Sim G. K., Efstratiadis A. The isolation of structural genes from libraries of eucaryotic DNA. Cell. 1978 Oct;15(2):687–701. doi: 10.1016/0092-8674(78)90036-3. [DOI] [PubMed] [Google Scholar]
  26. Marcu K. B., Valbuena O., Perry R. P. Isolation, purification, and properties of mouse heavy-chain immunoglobulin mRNAs. Biochemistry. 1978 May 2;17(9):1723–1733. doi: 10.1021/bi00602a022. [DOI] [PubMed] [Google Scholar]
  27. Maxam A. M., Gilbert W. Sequencing end-labeled DNA with base-specific chemical cleavages. Methods Enzymol. 1980;65(1):499–560. doi: 10.1016/s0076-6879(80)65059-9. [DOI] [PubMed] [Google Scholar]
  28. Nasmyth K. A., Tatchell K. The structure of transposable yeast mating type loci. Cell. 1980 Mar;19(3):753–764. doi: 10.1016/s0092-8674(80)80051-1. [DOI] [PubMed] [Google Scholar]
  29. Ono M., Cole M. D., White A. T., Huang R. C. Sequence organization of cloned intracisternal A particle genes. Cell. 1980 Sep;21(2):465–473. doi: 10.1016/0092-8674(80)90483-3. [DOI] [PubMed] [Google Scholar]
  30. Pays E., Van Meirvenne N., Le Ray D., Steinert M. Gene duplication and transposition linked to antigenic variation in Trypanosoma brucei. Proc Natl Acad Sci U S A. 1981 May;78(5):2673–2677. doi: 10.1073/pnas.78.5.2673. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Potter M. Antigen-binding myeloma proteins of mice. Adv Immunol. 1977;25:141–211. [PubMed] [Google Scholar]
  32. 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]
  33. Schnell H., Steinmetz M., Zachau H. G., Schechter I. An unusual translocation of immunoglobulin gene segments in variants of the mouse myeloma MPC11. Nature. 1980 Jul 10;286(5769):170–173. doi: 10.1038/286170a0. [DOI] [PubMed] [Google Scholar]
  34. Seidman J. G., Max E. E., Leder P. A kappa-immunoglobulin gene is formed by site-specific recombination without further somatic mutation. Nature. 1979 Aug 2;280(5721):370–375. doi: 10.1038/280370a0. [DOI] [PubMed] [Google Scholar]
  35. Shen-Ong G. L., Cole M. D. Differing populations of intracisternal A-particle genes in myeloma tumors and mouse subspecies. J Virol. 1982 May;42(2):411–421. doi: 10.1128/jvi.42.2.411-421.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
  37. Storb U., Arp B., Wilson R. Myeloma with multiple rearranged immunoglobulin kappa genes: only one kappa gene codes for kappa chains. Nucleic Acids Res. 1980 Oct 24;8(20):4681–4687. doi: 10.1093/nar/8.20.4681. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Strathern J. N., Spatola E., McGill C., Hicks J. B. Structure and organization of transposable mating type cassettes in Saccharomyces yeasts. Proc Natl Acad Sci U S A. 1980 May;77(5):2839–2843. doi: 10.1073/pnas.77.5.2839. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Thomas P. S. Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5201–5205. doi: 10.1073/pnas.77.9.5201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Varmus H. E., Quintrell N., Ortiz S. Retroviruses as mutagens: insertion and excision of a nontransforming provirus alter expression of a resident transforming provirus. Cell. 1981 Jul;25(1):23–36. doi: 10.1016/0092-8674(81)90228-2. [DOI] [PubMed] [Google Scholar]
  41. Walfield A. M., Storb U., Selsing E., Zentgraf H. Comparison of different rearranged immunoglobulin kappa genes of a myeloma by electronmicroscopy and restriction mapping of cloned DNA: implications for "allelic exclusion". Nucleic Acids Res. 1980 Oct 24;8(20):4689–4707. doi: 10.1093/nar/8.20.4689. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Wall R., Gilmore-Hebert M., Higuchi R., Komaromy M., Paddock G., Strommer J., Salser W. Recombinant DNA clones constructed from immunoglobulin kappa light chain messenger RNA. Nucleic Acids Res. 1978 Sep;5(9):3113–3128. doi: 10.1093/nar/5.9.3113. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Wilson R., Miller J., Storb U. Rearrangement of immunoglobulin genes. Biochemistry. 1979 Oct 30;18(22):5013–5021. doi: 10.1021/bi00589a032. [DOI] [PubMed] [Google Scholar]
  44. Wivel N. A., Smith G. H. Distribution of intracisternal A-particles in a variety of normal and neoplastic mouse tissues. Int J Cancer. 1971 Jan 15;7(1):167–175. doi: 10.1002/ijc.2910070119. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES