Many newly developed animal models involve the transfer of cells, serum or other tissue -derived products into live rodents. These biologicals and tissues can serve as repositories for adventitious rodent pathogens that, when used in animal studies, can alter research outcomes and result in endemic outbreaks. The different general rodent tumor model systems include injection of tumor cells which can be used to propagate tumor cell lines and to study various treatment regimens. Tumor cells can either be injected orthotopically, in the tissue or site of origin, or ectopically, usually by subcutaneous injection in the flanks of rodents or by IP or IV injection. Tumors can form spontaneously in specific inbred strains, spontaneous mutants or genetically engineered mice. These models are commonly used to study environmental and preventative therapeutic effects on tumor incidence and development, the specific genetically based mechanism resulting in tumor development and cancer therapies. Lastly, tumors in rodents can be induced by chemicals, radiation, inflammation or infection. Chemically induced tumor models are the most common and result from exposing the animal to a known and well documented carcinogen with predictable level of tumor induction.
Any materials injected into mice, especially human or rodent tissues, tumors or biologicals may be infected with viruses or mycoplasmas that can be infectious to humans or rodents and may be hazardous to human health. At least 16 rodent viruses, mycoplasmas, and protozoa are known to infect tumors: Lactate dehydrogenase-elevating virus (LDV- mice), Minute Virus of Mice (MVM-mice), Kilham’s Rat Virus (rats), Toolan’s H-1 parvovirus (mice, rats, humans), Rat Parvovirus (RPV-rats), Mouse Parvovirus (MPV-mice), Mouse Hepatitis Virus (MHV-mice), Lymphocytic Choriomeningitis Virus (LCMV-mouse, rat, hamster, human), Reovirus-3 (rodent, human), K virus (mouse), Polyoma virus (mouse), Sendai virus (mouse, rat), Adenovirus (mouse), Ectromelia virus (mouse), Hanta virus (mouse, rat, human), various Mycoplasma spp. (mouse, rat) and protozoa such as Encephalitozoon cuniculi.
Tissues and biological material may be infected with a variety of agents that may be infectious to humans or animals and potentially jeopardize the health of both. Additionally, contaminating pathogens may act as a confounding variable on research results. Therefore, testing should be conducted on cells, tissues and biologicals for rodent pathogens before they are injected or implanted into rodents housed in IUB animal facilities.
Targets
Materials to be screened include tumors, tissues, immortal cell lines, embryonic stem cells, serum and mammalian components of cell culture media used to culture cells that will be inoculated into rodents. In addition, all mammalian cells and tissues from a rodent source,
mammalian cells and tissues that have been passed through rodents or rodent cells without subsequent purification, non-mammalian agents cultured in rodents or rodent cells without subsequent purification. Biological specimens that should be tested include cells intended for hybridoma formation, tumor cells, cell culture media, viral or bacterial agents cultured in rodent cells or tissue, blood products including serum, antibodies, and viruses or viral vectors coming in contact with rodents. Lastly, cells and biological materials from ATCC require testing for murine viruses.
Testing
Screening of biological materials is done by direct or reverse transcriptase polymerase chain reaction (PCR) at the Research Animal Diagnostic and Investigative Laboratory (RADIL) of the University of Missouri. This technology replaces the antibody production test which involved the use of live animals and had a lengthy turnaround time (25-30 days). Cells, tissues or materials to be bested for mouse pathogens are tested in their Infectious Microbe PCR Amplification Test (IMPACT I). Testing at other vendors is possible but IUB prefers RADIL. Approximate costs for testing as of 12/12/19 are Mouse IMPACT I $642.00, and Rat IMPACT V. $457.00 with an approximate turnaround time of 1 week. Contact RADIL for more information about details for shipping.
Any biological materials of human origin require handling at the BSL2 or ABSL2 level with universal precautions and as blood-borne pathogens but do not need to be tested.
Testing results on mouse origin tissues for biological materials should be approved by LAR veterinarians before administering to rodents. Testing should be performed and approved by LAR veterinarians before placing in rodents housed in LAR Core Facilities. Rodents used as hosts for foreign tissue my also be housed in containment so that other rodents in nearby colonies aren’t subject to potential infections from these transplanted cells. For further information, please contact LAR veterinarians.