Not surprisingly, mice with compromised immune systems require special care and housing compared to immune-competent animals. Like all laboratory mice, they should be maintained in specific pathogen-free (SPF) rooms that are carefully monitored for the presence of mouse pathogens. For immunodeficient mice, however, the barrier level – that is, the restrictions on which organisms are permitted in the room – needs to be higher.
The specific nature of the animals’ immune deficiencies will dictate what additional care is required. Many inbred strains, including NOD/ShiLtJ, SWR/J and A/J mice are C5 (hemolytic) complement deficient (Hc<0>), but these mice thrive under standard-barrier conditions. C3H/HeJ and C57BL/10ScN mice, which are deficient in Tlr4, also do well under relatively low-barrier conditions, but care must be taken to minimize their exposure to gram-negative bacteria such as Pseudomonas and Helicobacter since these mice are more susceptible to infection from these pathogens than other strains.
Severely immunocompromised mice, such as nude (Foxn1<nu>), scid (Prkdc<scid>), Rag1-deficient (Rag1<tm1Mom>) and NSG (NOD.Cg-Prkdc<scid> Il2rg<tm1Wjl>/SzJ (005557)) mutant mice require very high barriers that exclude most organisms that infect mice, including many that normally do not evoke clinical illness in immune-competent animals . In addition, T cell receptor (TCR) transgenic mice such as OT-1 (C57BL/6-Tg(TcraTcrb)1100Mjb/J (003831)) and OT-2 (B6.Cg-Tg(TcraTcrb)425Cbn/J (004194)) mice should be housed under high barrier conditions. Although they have functional B and T cells, the transgenes that they carry direct expression of rearranged TCRs, which limits the T cell-based immune responses to one or only a few antigens. TCR transgenic mice, therefore, are significantly immunocompromised.
At JAX, our production rooms are divided among three barrier levels – “standard,” “high” and “maximum.” Severely immunocompromised mice are housed in maximum-barrier facilities. Below are the conditions that we recommend for housing the most severely immune-compromised animals:
• Use microisolator (filter bonneted) or pressurized, individually ventilated cages (PIV/IVC).
• Sterilize or disinfect food, water, bedding, cages and anything that will come in contact with the mice. Water should be acidified to pH2.5-3.0 to control Psuedomonas species contamination.
• Only personnel involved in care of the mice should have access to the mouse room, and caretakers should wear personal, protective equipment – sterile scrubs, frocks, gloves, masks and hair coverings – at all times. All skin surfaces should be covered to prevent the spread of bacteria to the mice.
• Cages should be changed under a laminar flow hood. Hands should be disinfected after opening the cage lid, reaching within the cage, or removing your gloved hands from the hood. Disinfect the hood between changes.
• Change cages weekly to prevent the introduction of minimal-inoculating doses of opportunistic or commensal organisms in the cage environment.
In general, we do not recommend treating mice, even immunodeficient mice, with antibiotics prophylactically. Such treatments are unnecessary if proper barrier conditions are maintained and may encourage the development of resistant pathogens. Under circumstances in which immunocompromised mice must be housed in a lower-barrier facility, then prophylactic treatment might be considered. Consult with your facilities veterinary staff for their recommendations.
The conditions listed above are ideal for maintaining immunocompromised mice. But suitable high-barrier rooms may not be available at all facilities, and space shortages may require housing immunodeficient strains under less than ideal conditions. For a review of procedures for establishing and maintaining as germ-free an environment as possible without the use of a barrier facility, see: RS Sedlacek et al., 1980, Development and operation of a stable limited defined flora mouse colony. Pp 197-201 in Animal Quality and Models in Biomedical Research, A. Spiegel et al., eds. Proceedings of the 7th Symposium of the International Council for Laboratory Animal Science (ICLAS) held August 21-23, 1979 in Utrecht, The Netherlands. Stuttgart: Gustav Fischer Verlag.
Another overall great resource on the care and husbandry of immunodeficient mice is “Immunodeficient Rodents: A Guide to Their Immunology, Husbandry and Use.” With careful handling and attention to the above details, your immunodeficient mice should lead a healthy and disease-free life!