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Both the United States and Canada have projected shortages of qualified laboratory-animal veterinarians within the next 10 years. This gap is occurring because of retirement, increased regulatory requirements for research animal oversight, and insufficient numbers of veterinarians entering this field. One of the primary means of increasing student interest in nontraditional practice areas, such as laboratory animal medicine, is to ensure that they have appropriate exposure to the topic during their basic clinical training. We outline a recommended curriculum for laboratory animal medicine for North American veterinary medical colleges, which provides strategies for integrating comparative medicine material into the curriculum, incorporates flexibility for a range of delivery methods, and suggests potential resources that may be used to develop this material. more...

Many factors influence ammonia levels in rodent cages, and high intracage ammonia has been associated with specific types of abnormal nasal pathology in mice. The use of autoclaved corncob bedding and the maintenance of low room humidity reduce the accumulation of ammonia in mouse cages. However, there are no engineering standards that define the limits of ammonia exposure for mice housed in static isolation cages. Regulatory guidance indicates that solid bottom cages must be sanitized at least weekly and that cage components in direct contact with animals must be sanitized at least every 2 wk. Common practice is to replace the bottoms and bedding of static isolation cages once weekly. To determine whether changing static isolation cages once weekly is an appropriate performance standard for mice, we prospectively evaluated the relationship between ammonia levels, nasal histopathology, and housing densities in various grouping strategies of mice housed in static isolation cages. Here, we report that the average nasal pathology score per cage and intracage ammonia levels were correlated, but nasal pathology scores did not differ among mice housed in breeding pairs, breeding trios, or female groups. In light of ammonia levels and histopathology scores as performance standards, these results suggest that a weekly cage-change frequency for static isolation cages does not result in adverse effects. Our results provide evidence to support current practices in the use of static isolation cages for housing laboratory mice in modern vivaria. more...

The advent of new scientific tools such as genetically manipulated rodents and mapping of the mouse genome has resulted in the use of reduced numbers of larger animals and in explosively growing populations of rodents (especially mice). At the same time, factors such as public concerns for animal wellness, availability, and costs for many traditionally used larger species have made their continued use more difficult to justify. As the total number of mice and rats used for research has increased, many individual rodents have become more valuable and many rodents are now more susceptible to disease. Because genetically manipulated rodents are enabling scientific investigators to answer a whole new universe of questions in vivo, we expect that the growth of rodent usage will continue for the next 5 to 10 yr. The purpose of this article is to describe the animal-related resources that we will need as we enter the 21st century to continue the progress of biomedical research. A discussion of future animal care needs is appropriate in this ILAR Journal issue devoted to opportunistic infections because many genetically manipulated rodents—the tools of the future— will be exquisitely sensitive to opportunistic infections. We postulate that major needs will exist for animals, staffing, and infrastructure to facilitate scientific progress between the time of this writing and 2010. more...

Publisher Summary The purpose of this chapter is to provide supplemental normative values and references for a number of the species. Some values may not be widely applicable to contemporary housing and husbandry conditions. The normative values presented here have been influenced by the laboratory test, animal source, animal genotype, age, gender, blood sampling method, use of anesthesia, or feed or housing conditions of the animals tested. Some normative values may have been derived from feral or newly confined animals. For this reason, it is always recommended that control tests be run concurrently with tests for animals that are suspected to be ill prior to making final diagnostic conclusions or selecting treatment regimens. more...

Summary Two day-old athymic (rnu/rnu) and euthymic (rnu/+) rat pups nursing immune or non-immune dams were inoculated oronasally with the Yale strain of rat virus (RV-Y). All athymic and euthymic pups (57/57) from immune dams remained clinically normal, whereas 51 of 66 athymic and euthymic pups from non-immune dams died within 30 days. Infectious RV was detected by explant culture in 12 of 15 surviving pups of both genotypes from non-immune dams 30 days after inoculation, but in none of the 57 surviving pups from immune dams. RV-Y DNA was detected by Southern blotting in kidneys of surviving athymic pups from non-immune dams but was not detected in pups from immune dams. Euthymic pups from immune dams appeared not to produce endogenous antibody to RV after virus challenge, whereas euthymic pups from non-immune dams produced high-titered RV immune serum. Pups of both genotypes given immune serum prior to or with RV were fully protected from disease and persistent infection, whereas pups given immune serum 24 hours after RV were partially protected. These studies show that RV antibody offers significant protection against lethal and persistent RV infection. more...

Publisher Summary This chapter covers health care delivery for individual mice, quality assurance (QA) programs for research colonies of mice, and infectious outbreak sources and management. Comprehensive health care must be provided in all of these areas to be effective. An unwanted infectious agent that does not cause clinically evident signs could still have a major adverse impact on research results if allowed to disseminate. As a result, the program for providing health care must include detection and care of individual mice that are ill, routine colony surveillance to guard against the undetected entry and spread of previously excluded infectious agents, and a response plan if such agents are detected. Such programs result in humane care of animals and the best protection of experimental repeatability and validity. As infectious agents, detection and treatment methods, and the research environment evolve, the veterinary and husbandry staff caring for research animals must strive to keep themselves educated and informed. Animal health and QA programs are not static but are always a work in progress and must also evolve in response to the challenges and needs of the research community. more...

Publisher Summary This chapter discusses the infections caused by DNA viruses and also RNA viruses. The chapter focuses on the detection, diagnosis, risk assessment, and decision-making regarding viral infections. Several infections caused by DNA viruses are parvoviruses, rat cytomegalovirus, poxviruses, adenovirus, and papovavirus. Several RNA viruses and infections caused by these viruses are coronaviruses, paramyxoviruses, rotavirus and reovirus, and picornaviruses. Monitoring for viral infections should cover at least three venues: animals in established breeding and experimental colonies, animals held in entry quarantine, and animal tissues and products destined for in vivo use. For established colonies, monitoring should be tailored to local conditions. Effective monitoring should encompass sampling on a pre-arranged schedule, which can be intensified if evidence or suspicion of viral infection emerges. Because viral infections of rats can spread insidiously, early detection and epidemiologic “staging” should employ a detection matrix that includes clinical observation, appropriate sampling, and sensitive and specific diagnostic testing. more...

Routine testing of bedding sentinels from a barrier room revealed one mouse seropositive to ectromelia virus (EV). Results of hemagglutination-inhibition testing and western blot analysis were confirmatory for orthopoxvirus antibodies. Additional seropositive animals were not identified. Interviews indicated that replication-competent vaccinia virus (VV), Western Reserve strain (VV-WR), recently had been given to mice. Although VV-WR was not expected to spread by contact or via fomites, the case evidence suggested transmission of vaccinia via soiled bedding. In a follow-up experiment, 15 index mice were inoculated with 10(7) plaque-forming units of VV by either subcutaneous or intrarectal instillation. A dedicated contact sentinel and a bedding sentinel were provided for each index mouse. All 15 index mice were positive for antibodies when tested 22 days after inoculation. One mouse, inoculated by the subcutaneous route, appeared ill and developed lesions on the proximal portion of the tail. The contact sentinel mouse housed with this index mouse was the only sentinel to seroconvert. We conclude that VV-WR can spread to contact sentinels and potentially to bedding sentinels. The ability of other VV strains to be transmitted horizontally and the susceptibility of different mouse strains to infection merit further investigation. The use of VV in animal facilities must be managed carefully since the available serologic tests do not distinguish between VV and EV, an exotic agent of major concern to laboratory animal facilities. more...

Animal-based research comprises almost half of the portfolio of the National Institutes of Health (NIH). It is vital to the biomedical community but is encountering unprecedented challenges to its continued success. These challenges are related to technological advances in science and to specific aspects of the regulatory climate and costs of animal research. These are not abstract issues for the individual scientist. The costs for animal research may determine in which institution a scientist pursues his/her research and with whom he/she can, or cannot, collaborate. The National Allergy and Infectious Disease Advisory Council outlined many of these challenges in a resolution forwarded to NIH Director Varmus in February 1996. As scientists who deal with this issue daily, we highlight the origins and the potential solutions. Much current animal-based research focuses on basic biological mechanisms or host-agent interactions and requires specific pathogen free, genetically uniform rodents, especially mice. Many are designer animals that offer a unique opportunity to understand the function of specific genes or to create rodent models that are susceptible to human pathogens. Animals with induced mutations may be unusually susceptible to infectious agents including some previously considered inconsequential. These designer rodents require intensive health monitoring and more sophisticated husbandry; as a result expenses for equipment and specialized animal care have increased significantly. Historically, the NIH supported the infrastructure of animal resource programs as an essential component that protected federal investments in biomedical research. This support included grants to train veterinarians in specialties central to animal-based studies: research skills, laboratory animal medicine, and comparative pathology. Training grants now preclude substantive clinical training leaving a potential deficit in clinical support that can only be met by highly skilled professionals. Federal support for animal diagnostic laboratories (microbiology, virology, and pathology) also has been discontinued. Ironically, this has occurred as the need for diagnostic support to protect the health of designer animals has escalated. The animal diagnostic laboratories represented a financial partnership between the federal funding agencies and the biomedical community. As financial demands on institutions have increased, they find it difficult to fund these essential programs alone, despite their critical importance in support of animal health. An additional hidden cost has resulted from the growth of organismal approaches to molecular genetics, especially utilizing the achievements of the Human Genome Project. This growth also has brought many scientists with little or no background in animal research to animal-based studies. These individuals often require training by animal resource staff and veterinarians to prepare them to perform animal experimentation appropriately and to comply with regulations governing animal welfare. Animal welfare is a vital concern for the public and the scientific community; as a result, animal experimentation is heavily regulated. Regulatory agencies require extensive documentation of virtually all activities that involve animal use, entailing additional effort from investigators, administrators, and animal resource staff. Animal resource staff spend many hours reviewing required animal care protocols for institutional animal care and use committees, counseling and training scientists and their staff, providing veterinary medical care, monitoring compliance, and dealing with a myriad of details, inspections, and reports required by regulatory and accrediting agencies. Although regulations continue to proliferate, the cost: benefit ratio has not been adequately assessed scientifically, ethically, or financially by society, legislators, and regulatory agencies. Probably the single most damaging action to affect the cost of animal research was the federal government’s decision to consider research animal resource programs as “specialized facilities.” This action required that all the costs of operating such facilities must be excluded from the institution’s indirect cost recovery agreement and instead should be fully recovered from users. The rationale underlying this approach appears flawed, because other types of regulated research, for example, that using radioactive isotopes, are not treated in this fashion. Federal negotiators have implemented the “specialized facility” rule inconsistently in apparently comparable institutions. When it is applied, the direct costs of animal research soar—often more than doubling ([1][1]). Coupled with the federal government’s increasing efforts to drive down the recovery of the indirect costs of research, the effect on an animal care program can be devastating. Ongoing efforts by the National Center for Research Resources (NCRR) to standardize the methodology for allocating costs of animal use are an important step as are the ongoing discussions with the Office of Management and Budget (OMB) that seek to redress this targeting of animal research. The draft for cost analysis and rate setting is available for comment until 12 May 1997 ( ). We have responsibilities for the oversight of laboratory animal programs in major research institutions. As investigative scientists we applaud the opportunities presented by animal research; as research animal program and animal facility administrators, we strive to find ways to achieve them. We cannot do this alone. We seek partnership with fellow scientists who use research animals, institutional leadership, an informed public, and the federal government. To remove penalties from animal research and benefit animal welfare, we recommend that the revised standards of cost allocation by OMB be adopted promptly and that the designation as “specialized facilities” be removed from animal resource programs. Requiring institutions to allocate animal care costs comparably would create a level playing field; institutions could bench mark their costs and identify areas to improve efficiency based on local conditions. To further enhance animal welfare, we recommend that increasing funds be allocated to support animal health infrastructure especially for specialized animal populations. We know of no national forum to exchange views or seek workable and timely solutions. A workshop planned by the NCRR is an important step in this direction. However, we believe that it is important that the scientific community be aware of the obstacles to continued productive animal-based research and join in overcoming them. 1. [↵][2]Federal Register 60 , 7107 (1997). [1]: #ref-1 [2]: #xref-ref-1-1 "View reference 1 in text" more...