Skip to main content
Wiley - PMC COVID-19 Collection logoLink to Wiley - PMC COVID-19 Collection
. 2011 Sep 6;36(1):33–39. doi: 10.1111/j.1600-0897.1996.tb00136.x

Maternal Antibodies Protect Immunoglobulin Deficient Neonatal Mice From Mouse Hepatitis Virus (MHV)‐Associated Wasting Syndrome

Erika Gustafsson 1,, Gunilla Blomqvist 2, Anna Bellman 2, Rikard Holmdahl 3, Anita Mattsson 1, Ragnar Mattsson 1
PMCID: PMC7159460  PMID: 8831899

Abstract

PROBLEM: Neonatal mice nursed by dams lacking immunoglobulins (Igs) may often suffer from lethal runting if raised under conventional conditions. The present study was performed in order to clarify a) the cause of the wasting syndrome and b) the protective role of antigen‐specific milk antibodies.

METHOD: Ig‐deficient mouse embryos in a conventional environment were embryo‐transferred to specified pathogen free (SPF) dams. Neonatal growth, mortality, and health status of mice from both environments was recorded. Suspected presence of mouse hepatitis virus (MHV) was tested by RT‐PCR. Protective effects on neonatal mortality of milk containing different titers of anti‐MHV antibodies were investigated in cross‐fostering experiments.

RESULTS: The SPF colony of Ig‐deficient mice exhibited no breeding problems, whereas Ig‐deficient neonates in the conventional environment suffered from lethal wasting syndrome. Serological screening of the mice kept in the two environments revealed that mice in the conventional room had high titers of antibodies against mouse hepatitis virus. Presence of MHV in runting neonates was confirmed by pathological examinations and RT‐nested‐PCR using MHV genome specific primers. Milk containing high titers of anti‐MHV antibodies, when provided for 8 days or more, completely prevented Ig‐deficient neonates from developing wasting syndrome in the conventional environment.

CONCLUSION: These findings show that the neonatal wasting syndrome is associated with the presence of MHV and that neonates are efficiently protected by MHV‐specific antibodies in the milk.

Keywords: Immunoglobulin‐deficient mice, immunoglobulins, lactation, milk, antibodies, mouse hepatitis virus, wasting syndrome

REFERENCES

  • 1. Burgio G., Ugazio AG, Notarangelo LD. Immunology of the neonate. Curr Opin Immunol 1990; 2: 770–777. [DOI] [PubMed] [Google Scholar]
  • 2. Brambell FWR. The transmission of passive immunity from mother to young, Amsterdam, North‐Holland, 1970. [Google Scholar]
  • 3. Mattsson R. Increase in the number of plaque forming cells with length of gestation in untreated pregnant mice. Dev Comp Immunol 1982; 6: 339–348. [DOI] [PubMed] [Google Scholar]
  • 4. Carter J., Dresser DW. Pregnancy induces an increase in the number of immunoglobulin‐secreting cells. Immunology 1983; 49: 481–490. [PMC free article] [PubMed] [Google Scholar]
  • 5. Bos NA, Benner R., Wostmann BS, Pleasants JR. Background of Ig‐secreting cells in pregnant mice fed a chemically defined ultrafiltered diet. J Reprod Immunol 1986; 9: 237–246. [DOI] [PubMed] [Google Scholar]
  • 6. Mattsson R., Mattsson A., Sulila P. Allogeneic pregnancy in B‐cell deprived mice: Effects on maternal lymphoid organs and fetal survival. Dev Comp Immunol 1985; 9: 709–717. [DOI] [PubMed] [Google Scholar]
  • 7. Rodger JC. Lack of requirement for a humoral immune response to establish or maintain successful allogeneic pregnancy. Transplantation 1985; 40: 372–375. [DOI] [PubMed] [Google Scholar]
  • 8. Gustafsson E., Mattsson A., Holmdahl R., Mattsson R. Pregnancy in B‐cell‐deficient mice: Post partum transfer of immunoglobulins prevents neonatal runting and death. Biol Reprod 1994; 51: 1173–1180. [DOI] [PubMed] [Google Scholar]
  • 9. Mattsson R., Gustafsson E., Holmdahl R. Reproduction in immunoglobulin‐ deficient mice: A role for transmitted IgG in neonatal growth. Reg Immunol 1994; 6: 334–337. [Google Scholar]
  • 10. Kraft LM. Viral diseases of the digestive system In The mouse in biomedical research. Foster HL, Smith JD, Fox JG. (eds.). New York, Academic Press, 1982, Vol II, pp 151–191. [Google Scholar]
  • 11. Barthold SW. Mouse hepatitis virus biology and epizootiology In Viral and mycoplasmal infections of laboratory rodents: Effects on biomedical research. Bhatt PN, Jacoby RO, Morse AC, III, New AE. (eds.). San Diego, Academic Press, 1986, pp 571–601. [Google Scholar]
  • 12. Lindsey JR. Prevalence of viral and mycoplasmal infections in laboratory rodents In Viral and mycoplasmal infections of laboratory rodents: Effects on biomedical research. Bhatt PN, Jacoby RO, Morse AC, III, New AE. (eds.). San Diego, Academic Press, 1986, pp 801–808. [Google Scholar]
  • 13. Caseboldt D., Lindsey JR, Cassell GH. Prevalence of infectious agents among commercial breeding populations of rats and mice. Lab Anim Sci 1988; 38: 327–329. [PubMed] [Google Scholar]
  • 14. Kraft V., Meyer B. Seromonitoring in small laboratory animal colonies. A five year survey: 1984–1988. Z Versuchtierk 1990; 33: 29–35. [PubMed] [Google Scholar]
  • 15. Keck JG, Makino S., Soe LH, Fleming JO, Stohlman SA, Lai MMC. RNA recombination of coronavirus. Adv Exp Med Biol 1987; 218: 99–107. [DOI] [PubMed] [Google Scholar]
  • 16. Kitamura D., Roes J., Kühn R., Rajewsky K. A B cell‐deficient mouse by targeted disruption of the membrane exon of immunoglobulin μ chain gene. Nature 1991; 350: 423–426. [DOI] [PubMed] [Google Scholar]
  • 17. Zijlstra M., Li E., Sajjadi F., Subramani S., Jaenisch R. Germline transmission of a disrupted β2‐microglobulin gene produced by homologous recombination in embryonic stem cells. Nature 1989; 342: 435–438. [DOI] [PubMed] [Google Scholar]
  • 18. Ziljstra M., Bix M., Simister NE, Loring JM, Raulet DH, Jaenisch R. β2‐ microglobulin deficient mice lack CD48+ cytolytic T cells. Nature 1990; 344: 742–746. [DOI] [PubMed] [Google Scholar]
  • 19. Koller BH, Marrack P., Kappler JW, Smithies O. Normal development of mice deficient in b2M MHC class I protein, and CD8+T cells. Science 1990; 248: 1227–1230. [DOI] [PubMed] [Google Scholar]
  • 20. Grusby MJ, Johnson RS, Papaioannou VE, Glimcher LH. Depletion of CD4+ T cells in major histocompatibility complex class II ‐ deficient mice. Science 1991; 253: 1417–1420. [DOI] [PubMed] [Google Scholar]
  • 21. Hogan B., Costantini F., Lacy E. Manipulating the mouse embryo: A laboratory manual, Cold Spring Harbor, Cold Spring Harbor Press, 1986. [Google Scholar]
  • 22. Engvall E. Enzyme immunoassay ELISA and EMIT. Enzymology 1980; 70: 419–439. [DOI] [PubMed] [Google Scholar]
  • 23. Jacoby RO, Fox JG. Biology and Diseases of Mice In Laboratory animal medicine. Fox JG, Cohen BJ, Loew FM. (eds.). Orlando, Academic Press, 1984, pp 49–78. [Google Scholar]
  • 24. Sebesteny M., Hill A. Hepatitis and brain lesions due to mouse hepatitis virus accompained by wasting in nude mice. Lab Anim Sci 1974; 8: 317–326. [DOI] [PubMed] [Google Scholar]
  • 25. Croy BA, Percy DA. Diagnostic exercise: Viral hepatitis in SCID mice. Lab Anim Sci 1993; 43: 193–194. [PubMed] [Google Scholar]
  • 26. Compton SR, Barthold SW, Smith AL. The cellular and molecular pathogenesis of coronaviruses. Lab Anim Sci 1993; 43: 15–28. [PubMed] [Google Scholar]
  • 27. Barthold SW, Smith AL, Lord FS, Jacoby RO, Main AJ. Epizootic coronaviral typhocolitis in suckling mice. Lab Anim Sci 1982; 32: 376–383. [PubMed] [Google Scholar]
  • 28. Pickel K., Muller MA, Ter Meulen V. Influence on maternal immunity on the outcome of murine coronavirus JHM infection in suckling mice. Med Microbiol Immunol 1985; 174: 15–24. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 29. Homberger FR, Barthold SW. Passively acquired challenge immunity to enterotropic coronavirus in mice. Arch Virol 1992; 126: 35–43. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 30. Ishida T., Fujiwara K. Maternally derived immunity resistance to fatal diarrhea in infant mice to mouse hepatitis virus. Jpn J Exp Med 1982; 52: 231–235. [PubMed] [Google Scholar]
  • 31. Barthold SW, Beck DS, Smith AL. Mouse hepatitis virus and host determinants of vertical transmission and maternally derived passive immunity in mice. Arch Virol 1988; 100: 171–183. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 32. Hierholzer JC, Broderson JR, Murphy FA. New strain of mouse hepatitis virus as cause of lethal enteritis in infant mice. Infect Immun 1979; 24: 508–522. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from American Journal of Reproductive Immunology are provided here courtesy of Wiley

RESOURCES