Skip to main content
PMC home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1978 Mar 1;147(3):854–871. doi: 10.1084/jem.147.3.854

Genetic studies of autoimmunity and retrovirus expression in crosses of New Zealand black mice I. Xenotropic virus

PMCID: PMC2184200  PMID: 204726

Abstract

The relationship between expression of xenotropic virus and the development of autoimmunization was studied in the progeny of crosses between New Zealand Black (NZB) and SWR mice. The (F1 X SWR) and F2 progeny segregated into three phenotypes: high-virus, low-virus, and virus-negative; F1 and (F1 X NZB) progeny were always high-virus. Autoantibodies, immune deposit nephritis and lymphomas developed in the progeny of these crosses. The virological phenotype of the animal could be dissociated from the presence of either autoantibodies or nephritis. For example, mice that expressed titers of virus as high as the NZB parent failed to develop signs of autoimmunization, even up to 24 mo of age. By contrast, some (F1 X SWR) and F2 mice that expressed low titers of virus developed autoimmune disease. Furthermore, a proportion of virus-negative mice produced autoantibodies and were found to have typical immune deposit nephritis. No viral antigens could be detected in the renal lesions of such virus-negative animals. By contrast with the dissociation between expression of virus and occurrence of nephritis, the presence of antibodies to DNA correlated with the development of renal lesions. We conclude that the genes that determine the expression of infectious xenotropic virus in NZB mice segregate independently from those that are involved in the autoimmune disease of these animals.

Full Text

The Full Text of this article is available as a PDF (1.8 MB).

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. 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]
  3. 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]
  4. Channing A. A., Kasuga T., Horowitz R. E., Dubois E. L., Demopoulos H. B. An ultrastructural study of spontaneous lupus nephritis in the NZB-BL-NZW mouse. Am J Pathol. 1965 Oct;47(4):677–694. [PMC free article] [PubMed] [Google Scholar]
  5. Datta S. K., McConahey P. J., Manny N., Theofilopoulos A. N., Dixon F. J., Schwartz R. S. Genetic studies of autoimmunity and retrovirus expression in crosses of New Zealand black mice. II. The viral envelope glycoprotein gp70. J Exp Med. 1978 Mar 1;147(3):872–881. doi: 10.1084/jem.147.3.872. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. 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]
  7. Datta S. K., Schwartz R. S. Mendelian segregation of loci controlling xenotropic virus production in NZB crosses. Virology. 1977 Dec;83(2):449–452. doi: 10.1016/0042-6822(77)90193-3. [DOI] [PubMed] [Google Scholar]
  8. Datta S. K., Schwartz R. S. Susceptibility to lymphomas and expression of C-type RNA viruses during the graft versus host reaction. Eur J Cancer. 1976 Dec;12(12):977–988. doi: 10.1016/0014-2964(76)90064-5. [DOI] [PubMed] [Google Scholar]
  9. DeHeer D. H., Edgington T. S. Evidence for a B lymphocyte defect underlying the anti-X anti-erythrocyte autoantibody response of NZB mice. J Immunol. 1977 May;118(5):1858–1863. [PubMed] [Google Scholar]
  10. Del Vellano B. C., Nave B., Croker B. P., Lerner R. A., Dixon F. J. The oncornavirus glycoprotein gp69/71: a constituent of the surface of normal and malignant thymocytes. J Exp Med. 1975 Jan 1;141(1):172–187. doi: 10.1084/jem.141.1.172. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Dixon F. J., Oldstone M. B., Tonietti G. Pathogenesis of immune complex glomerulonephritis of New Zealand mice. J Exp Med. 1971 Sep 1;134(3 Pt 2):65s–71s. [PubMed] [Google Scholar]
  12. Dunn T. B., Deringer M. K. Reticulum cell neoplasm, type B, or the "Hodgkin's-like lesion" of the mouse. J Natl Cancer Inst. 1968 Apr;40(4):771–821. [PubMed] [Google Scholar]
  13. East J., Harvey J. J., Tilly R. Transmission of auto-immune haemolytic anaemia and murine leukaemia virus in NZB-BALB/c hybrid mice. Clin Exp Immunol. 1976 Apr;24(1):196–209. [PMC free article] [PubMed] [Google Scholar]
  14. Feldman D. C-type virus particle formation in erythroblastic islands in spleens of C3Hf mice injected with erythropoietin. Proc Natl Acad Sci U S A. 1976 Oct;73(10):3710–3713. doi: 10.1073/pnas.73.10.3710. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Fischinger P. J., Blevins C. S., Nomura S. Simple, quantitative assay for both xenotropic murine leukemia and ecotropic feline leukemia viruses. J Virol. 1974 Jul;14(1):177–179. doi: 10.1128/jvi.14.1.177-179.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. 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]
  17. Gillespie D., Gallo R. C. RNA processing and RNA tumor virus origin and evolution. Science. 1975 May 23;188(4190):802–811. doi: 10.1126/science.47650. [DOI] [PubMed] [Google Scholar]
  18. Gold E. Clumping and sedimentation patterns: manifestations of haemagglutination. Vox Sang. 1968;15(3):222–231. doi: 10.1111/j.1423-0410.1968.tb01753.x. [DOI] [PubMed] [Google Scholar]
  19. Hartley J. W., Rowe W. P. Naturally occurring murine leukemia viruses in wild mice: characterization of a new "amphotropic" class. J Virol. 1976 Jul;19(1):19–25. doi: 10.1128/jvi.19.1.19-25.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. 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]
  21. Kawashima K., Ikeda H., Hartley J. W., Stockert E., Rowe W. P., Old L. J. Changes in expression of murine leukemia virus antigens and production of xenotropic virus in the late preleukemic period in AKR mice. Proc Natl Acad Sci U S A. 1976 Dec;73(12):4680–4684. doi: 10.1073/pnas.73.12.4680. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Lerner R. A., Wilson C. B., Villano B. C., McConahey P. J., Dixon F. J. Endogenous oncornaviral gene expression in adult and fetal mice: quantitative, histologic, and physiologic studies of the major viral glycorprotein, gp70. J Exp Med. 1976 Jan 1;143(1):151–166. doi: 10.1084/jem.143.1.151. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Levy J. A., Datta S. K., Schwartz R. S. Recovery of xenotropic virus but not ecotropic virus during graft-versus-host reaction in mice. Clin Immunol Immunopathol. 1977 Mar;7(2):262–268. doi: 10.1016/0090-1229(77)90053-8. [DOI] [PubMed] [Google Scholar]
  24. Levy J. A., Kazan P., Varnier O., Kleiman H. Murine xenotropic type C viruses I. Distribution and further characterization of the virus in NZB mice. J Virol. 1975 Oct;16(4):844–853. doi: 10.1128/jvi.16.4.844-853.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Levy J. A. Xenotropic C-type viruses and autoimmune disease. J Rheumatol. 1975 Jun;2(2):135–148. [PubMed] [Google Scholar]
  26. Lewis R. M., Armstrong M. Y., André-Schwartz J., Muftuoglu A., Beldotti L., Schwartz R. S. Chronic allogeneic disease. I. Development of glomerulonephritis. J Exp Med. 1968 Oct 1;128(4):653–679. doi: 10.1084/jem.128.4.653. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Lewis R. M., Stollar B. D., Goldberg E. B. A rapid, sensitive test for the detection of antibodies to DNA. J Immunol Methods. 1973 Dec;3(4):365–374. doi: 10.1016/0022-1759(73)90038-0. [DOI] [PubMed] [Google Scholar]
  28. Markham R. V., Jr, Sutherland J. C., Mardiney M. R., Jr The ubiquitous occurrence of immune complex localization in the renal glomeruli of normal mice. Lab Invest. 1973 Jul;29(1):111–120. [PubMed] [Google Scholar]
  29. Melief C. J., Datta S. K., Louie S., Johnson S., Melief M., Schwartz R. S. Splenocyte plaque assay for the detection of murine leukemia virus. Proc Soc Exp Biol Med. 1975 Sep;149(4):1015–1018. doi: 10.3181/00379727-149-38946. [DOI] [PubMed] [Google Scholar]
  30. Oldstone M. B., Dixon F. J. Pathogenesis of chronic disease associated with persistent lymphocytic choriomeningitis viral infection. I. Relationship of antibody production to disease in neonatally infected mice. J Exp Med. 1969 Mar 1;129(3):483–505. doi: 10.1084/jem.129.3.483. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Rowe W. P., Pincus T. Quantitative studies of naturally occurring murine leukemia virus infection of AKR mice. J Exp Med. 1972 Feb 1;135(2):429–436. doi: 10.1084/jem.135.2.429. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Schwartz R. S. Virsues and systemic lupus erythematosus. N Engl J Med. 1975 Jul 17;293(3):132–136. doi: 10.1056/NEJM197507172930308. [DOI] [PubMed] [Google Scholar]
  33. Stephension J. R., Reynolds R. K., Tronick S. R., Aaronson S. A. Distribution of three classes of endogenous type-C RNA viruses among inbred strains of mice. Virology. 1975 Oct;67(2):404–414. doi: 10.1016/0042-6822(75)90442-0. [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. Todaro G. J., Sherr C. J., Benveniste R. E., Lieber M. M., Melnick J. L. Type C viruses of baboons: isolation from normal cell cultures. Cell. 1974 May;2(1):55–61. doi: 10.1016/0092-8674(74)90008-7. [DOI] [PubMed] [Google Scholar]
  36. Tung J. S., Fleissner E., Vitetta E. S., Boyse E. A. Expression of murine leukemia virus envelope glycoprotein gp69/71 on mouse thymocytes. Evidence for two structural variants distinguished by presence vs. absence of GIX antigen. J Exp Med. 1975 Aug 1;142(2):518–523. doi: 10.1084/jem.142.2.518. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Vincent R. N., Mukherjee B. B., Mobry P. M., Bartok K. Changes in transcription of endogenous type-C virus genome during mouse liver regeneration. J Gen Virol. 1976 Dec;33(3):411–419. doi: 10.1099/0022-1317-33-3-411. [DOI] [PubMed] [Google Scholar]
  38. Yoshiki T., Mellors R. C., Strand M., August J. T. The viral envelope glycoprotein of murine leukemia virus and the pathogenesis of immune complex glomerulonephritis of New Zealand mice. J Exp Med. 1974 Oct 1;140(4):1011–1027. doi: 10.1084/jem.140.4.1011. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES