Skip to main content
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1978 May 1;147(5):1487–1502. doi: 10.1084/jem.147.5.1487

Genetic studies in NZB mice. I. Spontaneous autoantibody production

PMCID: PMC2184274  PMID: 418139

Abstract

The appearance of naturally occurring thymocytotoxic autoantibodies (NTA) and spontaneously produced antibodies to single-stranded DNA (ssDNA) was studied in NZB, and DBA/2 mice and their F1 and backcross progeny. NTA production was markedly decreased in males; however, castrated males produced quantities of NTA similar to those of females. Because the amount of NTA was influenced by sex hormones, it was necessary to gonadectomize all progeny to determine the mode of inheritance. Such studies suggested that NTA production was determined by a single locus with a gene dosage (codominant) mode of expression. The spontaneous production of antibodies to ssDNA appeared to be inherited as a single dominant genetic trait. The quantity of anti- ssDNA was also found to be under additional regulation; either a gene dosage effect or more likely a regulatory gene. The genes controlling the presence and quantity of ssDNA antibodies were not linked to the gene controlling the appearance of NTA.

Full Text

The Full Text of this article is available as a PDF (960.8 KB).

Selected References

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

  1. BIELSCHOWSKY M., BIELSCHOWSKY F. OBSERVATIONS ON NZB/B1 MICE; DIFFERENTIAL FERTILITY IN RECIPROCAL CROSSES AND THE TRANSMISSION OF THE AUTO-IMMUNE HAEMOLYTIC ANAEMIA TO NZB/B1 X NZC/B1 HYBRIDS. Aust J Exp Biol Med Sci. 1964 Aug;42:561–568. [PubMed] [Google Scholar]
  2. Biozzi G., Asofsky R., Lieberman R., Stiffel C., Mouton D., Benacerraf B. Serum concentrations and allotypes of immunoglobulins in two lines of mice genetically selected for "high" or "low" antibody synthesis. J Exp Med. 1970 Oct 1;132(4):752–764. doi: 10.1084/jem.132.4.752. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Braverman I. M. Study of autoimmune disease in New Zealand mice. I. Genetic features and natural history of NZB, NZY and NZW strains and NZB-NZW hybrids. J Invest Dermatol. 1968 Jun;50(6):483–499. doi: 10.1038/jid.1968.79. [DOI] [PubMed] [Google Scholar]
  4. Burnet M., Holmes M. C. Genetic investigations of autoimmune disease in mice. Nature. 1965 Jul 24;207(995):368–371. doi: 10.1038/207368a0. [DOI] [PubMed] [Google Scholar]
  5. Datta S. K., Schwartz R. S. Genetics of expression of xenotropic virus and autoimmunity in NZB mice. Nature. 1976 Sep 30;263(5576):412–415. doi: 10.1038/263412b0. [DOI] [PubMed] [Google Scholar]
  6. Deheer D. H., Edginton T. S. Cellular events associated with the immunogenesis of anti-erythrocyte autoantibody responses of NZB mice. Transplant Rev. 1976;31:116–155. doi: 10.1111/j.1600-065x.1976.tb01453.x. [DOI] [PubMed] [Google Scholar]
  7. Eidinger D., Garrett T. J. Studies of the regulatory effects of the sex hormones on antibody formation and stem cell differentiation. J Exp Med. 1972 Nov 1;136(5):1098–1116. doi: 10.1084/jem.136.5.1098. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Fernandes G., Yunis E. J., Good R. A. Age and genetic influence on immunity in NZB and autoimmune-resistant mice. Clin Immunol Immunopathol. 1976 Nov;6(3):318–333. doi: 10.1016/0090-1229(76)90085-4. [DOI] [PubMed] [Google Scholar]
  9. Gasser D. L. Genetic control of the immune response in mice. I. Segregation data and localization to the fifth linkage group of a gene affecting antibody production. J Immunol. 1969 Jul;103(1):66–70. [PubMed] [Google Scholar]
  10. Gelfand M. C., Parker L. M., Steinberg A. D. Mechanism of allograft rejection in New Zealand mice. II. Role of a serum factor. J Immunol. 1974 Jul;113(1):1–8. [PubMed] [Google Scholar]
  11. Ghaffar A., Playfair J. H. The genetic basis of autoimmunity in NZB mice studied by progeny-testing. Clin Exp Immunol. 1971 Mar;8(3):479–490. [PMC free article] [PubMed] [Google Scholar]
  12. Holmes M. C., Burnet F. M. The characteristics of F1 and backcross hybrids between "high leukaemia" (AKR) and "autoimmune" (NZB) mouse strains. Aust J Exp Biol Med Sci. 1966 Jun;44(3):235–249. doi: 10.1038/icb.1966.24. [DOI] [PubMed] [Google Scholar]
  13. Howie J. B., Helyer B. J. The immunology and pathology of NZB mice. Adv Immunol. 1968;9:215–266. doi: 10.1016/s0065-2776(08)60444-7. [DOI] [PubMed] [Google Scholar]
  14. Klassen L. W., Krakauer R. S., Steinberg A. D. Selective loss of suppressor cell function in New Zealand mice induced by NTA. J Immunol. 1977 Sep;119(3):830–830. [PubMed] [Google Scholar]
  15. Knight J. G., Adams D. D., Purves H. D. The genetic contribution of the NZB mouse to the renal disease of the NZB x NZW hybrid. Clin Exp Immunol. 1977 May;28(2):352–358. [PMC free article] [PubMed] [Google Scholar]
  16. Lambert P. H., Dixon F. J. Pathogenesis of the glomerulonephritis of NZB/W mice. J Exp Med. 1968 Mar 1;127(3):507–522. doi: 10.1084/jem.127.3.507. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Lieberman R., Stiffel C., Asofsky R., Mouton D., Biozzi G., Benacerraf B. Genetic factors controlling anti-sheep erythrocyte antibody response and immunoglobulin synthesis in backcross and F2 progeny of mice genetically selected for "high" or "low" antibody synthesis. J Exp Med. 1972 Oct 1;136(4):790–798. doi: 10.1084/jem.136.4.790. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Mozes E., Fuchs S. Linkage between immune response potential to DNA and X chromosome. Nature. 1974 May 10;249(453):167–168. doi: 10.1038/249167a0. [DOI] [PubMed] [Google Scholar]
  19. Mozes E., McDevitt H. O., Jaton J. C., Sela M. The nature of the antigenic determinant in a genetic control of the antibody response. J Exp Med. 1969 Sep 1;130(3):493–504. doi: 10.1084/jem.130.3.493. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Papoian R., Pillarisetty R., Talal N. Immunological regulation of spontaneous antibodies to DNA and RNA. II. Sequential switch from IgM to IgG in NZB/NZW F1 mice. Immunology. 1977 Jan;32(1):75–79. [PMC free article] [PubMed] [Google Scholar]
  21. Parker L. M., Chused T. M., Steinberg A. D. Immunofluorescence studies on thymocytotoxic antibody from New Zealand Black mice. J Immunol. 1974 Jan;112(1):285–292. [PubMed] [Google Scholar]
  22. Raff M. C. Naturally-occurring autoantibodies to mouse thymocytes. Isr J Med Sci. 1971 Jun;7(6):724–726. [PubMed] [Google Scholar]
  23. Raveche E. S., Klassen L. W., Steinberg A. D. Sex differences in formation of anti-T-cell antibodies. Nature. 1976 Sep 30;263(5576):415–416. doi: 10.1038/263415a0. [DOI] [PubMed] [Google Scholar]
  24. Roubinian J. R., Papoian R., Talal N. Androgenic hormones modulate autoantibody responses and improve survival in murine lupus. J Clin Invest. 1977 Jun;59(6):1066–1070. doi: 10.1172/JCI108729. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Roubinian J. R., Papoian R., Talal N. Effects of neonatal thymectomy and splenectomy on survival and regulation of autoantibody formation in NZB/NZW F1 mice. J Immunol. 1977 May;118(5):1524–1529. [PubMed] [Google Scholar]
  26. Shirai T., Mellors R. C. Natural cytotoxic autoantibody against thymocytes in NZB mice. Clin Exp Immunol. 1972 Sep;12(1):133–152. [PMC free article] [PubMed] [Google Scholar]
  27. Shirai T., Mellors R. C. Natural thymocytotoxic autoantibody and reactive antigen in New Zealand black and other mice. Proc Natl Acad Sci U S A. 1971 Jul;68(7):1412–1415. doi: 10.1073/pnas.68.7.1412. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Shirai T., Yoshiki T., Mellors R. C. Age-decrease of cells sensitive to an autoantibody-specific for thymocytes and thymus-dependent lymphocytes in NZB mice. Clin Exp Immunol. 1972 Dec;12(4):455–464. [PMC free article] [PubMed] [Google Scholar]
  29. Silver D. M., McKenzie I. F., Winn H. J. Variations in the responses of C57BL-10J and A-J mice to sheep red blood cells. J Exp Med. 1972 Nov 1;136(5):1063–1071. doi: 10.1084/jem.136.5.1063. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Steinberg A. D., Klassen L. W. Role of suppressor T cells in lymphopoietic disorders. Clin Haematol. 1977 Jun;6(2):439–478. [PubMed] [Google Scholar]
  31. Steinberg A. D., Pincus T., Talal N. DNA-binding assay for detection of anti-DNA antibodies in NZB-NZW F1 mice. J Immunol. 1969 Mar;102(3):788–790. [PubMed] [Google Scholar]
  32. Steinberg A. D., Pincus T., Talal N. The pathogenesis of autoimmunity in New Zealand mice. 3. Factors influencing the formation of anti-nucleic acid antibodies. Immunology. 1971 Apr;20(4):523–531. [PMC free article] [PubMed] [Google Scholar]
  33. Talal N. Disordered immunologic regulation and autoimmunity. Transplant Rev. 1976;31:240–263. doi: 10.1111/j.1600-065x.1976.tb01456.x. [DOI] [PubMed] [Google Scholar]
  34. Talal N., Steinberg A. D. The pathogenesis of autoimmunity in New Zealand black mice. Curr Top Microbiol Immunol. 1974;64(0):79–103. doi: 10.1007/978-3-642-65848-8_3. [DOI] [PubMed] [Google Scholar]
  35. Terres G., Morrison S. L., Habicht G. S. A quantitative difference in the immune response between male and female mice. Proc Soc Exp Biol Med. 1968 Mar;127(3):664–667. doi: 10.3181/00379727-127-32768. [DOI] [PubMed] [Google Scholar]
  36. WASI P., BLOCK M. The histopathologic study of the development of the irradiation-induced leukemia in C57BL mice and of its inhibition by testosterone. Cancer Res. 1961 May;21:463–473. [PubMed] [Google Scholar]
  37. Warner N. L. Genetic control of spontaneous and induced antierythrocyte autoantibody production in mice. Clin Immunol Immunopathol. 1973 Apr;1(3):353–363. doi: 10.1016/0090-1229(73)90052-4. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES