Immunodeficient mice and susceptibility to Pneumocystis carinii
By H.G. Bedigian, Ph.D.
Susceptibility to opportunistic organisms
Pneumocystis carinii is a ubiquitous opportunistic organism that causes severe pulmonary disease in mice and other vertebrate species with acquired or inherited immune deficient syndromes. 1,2 The organism is not diagnosed in animals with a functional immune system. Mice with certain heritable or induced immunological defects are highly susceptible to infection with opportunistic organisms such as P. carinii.
Monitoring P. carinii
In our production facility, several immunodeficient strains, including BALB/cByJSmn-scid/J, are raised for distribution. The various immunodeficient strains are tested on a regular basis for the presence of P. carinii. Quarterly monitoring of random samples has been done for several years and no positive cases have been observed in strains maintained in our production facility. Lung sections from immunodeficient strains are examined by immunoperoxidase staining or by Gomori's silver staining.1 Because these mice are immunologically deficient and the method involves euthanizing the mice to be tested, we cannot certify that all mice in the colony are free of P. carinii. We also cannot guarantee that once mice leave our barrier facility they will not be exposed to P. carinii or other opportunistic organisms and develop clinical disease.
Reduced lifespan of immunodeficient mice housed in conventional animal rooms
Mice homozygous for the mutation severe combined immune deficiency (scid) are deficient in both humoral and cell-mediated immune function and lack detectable levels of circulating immunoglobulin.4 Despite the lack of functional lymphocytes, scid/scid mice survive up to 1 year of age or more under specific pathogen-free (SPF) conditions. However, the lifespan of scid mice maintained in conventional animal rooms is greatly reduced, most likely due to exposure of opportunistic organisms.
Leakiness of circulating antibodies
As stated above, mice carrying the scid mutation lack circulating antibodies. However, some scid mice appear to be "leaky" in that circulating Ig can be detected by 3 to 4 months of age.3 We have tested 7 BALB/cByJSmn-scid/J mice (3 months to 6 months of age) for the presence of serum Ig. The sera were assayed by ELISA and Ouchterlony methods. Circulating immunoglobulin (Ig+) was detected in two mice (one 3 months of age, the other 6) using both assays. Some factors that may influence this phenotype are the strain on which the mutation is placed, age of the animal and the environment in which the mice are housed. It is also important to realize that the Ig+ phenotype is not transmitted in a Mendelian fashion.4
1. Sundberg, J.P., T. Burnstein, L.D. Shultz, H.G. Bedigian. 1989. Identification of Pneumocystis carinii in immunodeficient mice. Lab Anim. Sci. 39:213-218.
2. Shultz, L.D., P.A. Schweitzer, E.J.Hall, J.P. Sundberg, S. Taylor, and P.D. Walzer. 1989. Pneumocystis carinii pneumonia in scid/scid mice. Curr. Topics Microbiol Immunol. 152:243-249.
3. Bosma, G.C., R.P. Custer, and M.J. Bosma. 1983. A severe combined immunodeficiency mutation in the mouse. Nature 301:527-530.
4. Bosma, G.C., M. Fried, R.P. Custer, A. Carroll, D.M. Gibson, and M.J. Bosma. 1988. Evidence of functional lymphocytes in some (leaky) scid mice. J. Exp. Med. 167:1016-1033.