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Microbial Status and Genetic Evaluation of Mice and Rats: Proceedings of the 1999 US/Japan Conference (2000)
Institute for Laboratory Animal Research (ILAR)

Page
142
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Microbial Status and Genetic Evaluation of Mice and Rats: PROCEEDINGS OF THE 1999 US/JAPAN CONFERENCE

Concluding Comments

John Strandberg

National Center for Research Resources

Bethesda, MD

My summary will be very brief because my review will cover the broad range of topics discussed during this ambitious program. We started by addressing the issue of microbiologic testing, and Dr. Shek recommended standardization by constant improvement, rather than setting up a regulatory-based mechanism to achieve microbiologic testing standards. He gave good reasons for doing this, including the continuing recognition of new agents as well as new methods for diagnosis.

Dr. Riley, talking about the standardization of tests, outlined a very exciting program in which they are now engaged in a first phase. This program uses standard specimens to determine the capability or accuracy of individual laboratories and to develop standard operating procedures, which I believe have been needed for a long time. From my perspective, this development is a very positive and important step.

Dr. Itoh then discussed factors that cause a lack of uniformity in results. His discussion was based on encounters in the EQUEST monitoring center with discrepancies between several specific agents such as Pasteurella pneumotropica and hemorrhagic fever with renal syndrome. He recommended that in harmonizing the tests, the methods must be enumerated along with the recommendations for their usefulness.

Dr. Shibahara described laboratories in Japan, which include 53 national university animal centers plus centers in private universities and municipalities and prefectures. He outlined a concern about international transfer of transgenic and knockout mice, which complicates the worldwide situation considerably. He noted that animals rejected for entry into Japanese laboratories because of infec

Page
142
Front Matter (R1-R16)
Opening Remarks, Judith Vaitukaitis (1-3)
Opening Remarks, Shin-Ichi Ota (4-5)
Introductory Comments on Microbiologic Testing of Laboratory Mice and Rats: Uniformity of Results (6-6)
Development of a Performance Assessment Program for Research Animal Diagnostic Laboratories and Defining Microbiologic Testing Standards (7-10)
Standardization of Rodent Health Surveillance: Regulation Versus Competition (11-15)
Factors Causing Difficulties in Uniformity of Results Among Testing Facilities in Microbiologic Monitoring of Laboratory Animals (16-20)
Necessity of Reexamining the Pathogenicity and Elimination of Parasites in Rats and Mice (21-26)
Emerging (and Reemerging) Viruses of Laboratory Mice and Rats (27-34)
Emerging Infections as a Cause of Concern (35-39)
Emerging Diseases in Mice and Rats (40-43)
Survey of Heliobacter Species in Laboratory Mice and Gerbils in Japan (44-46)
Genetic Evaluation of Outbred Rats (47-50)
Genetic Evaluation of Outbred Rats from the Breeder's Perspective (51-64)
Concept for Establishment of Rat Outbred Global Standard Strains (65-76)
Necessity of Genetic and Microbiologic Quality Network from the Pharmaceutical Industry's Perspective (77-84)
International Harmonization of Laboratory Animals (85-96)
Rat Genetics and Toxicology (97-104)
A Phenotype-driven Approach to the Molecular and Functional Analysis of the Mouse Genome (105-115)
Evaluation of Targeted Mutations (116-118)
Defining Behavioral Phenotypes in Transgenic and Knockout Mice (119-129)
Defining Phenotype in Genetically Engineered Mice (130-131)
Development of the Mouse Model Dramatype for Human Clinical Benefit (132-136)
Concluding Remarks (137-137)
Implication of Wild-derived Genes, Mitochondria, and Chromosomes in the Genetic Background of Mouse Models for Diseases and Biologic Functions (138-141)
Concluding Comments, John Strandberg (142-143)
Concluding Remarks, John Vandenbergh (144-146)
Appendix A (147-148)
Appendix B (149-150)

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OCR for page 142
Microbial Status and Genetic Evaluation of Mice and Rats: PROCEEDINGS OF THE 1999 US/JAPAN CONFERENCE Concluding Comments John Strandberg National Center for Research Resources Bethesda, MD My summary will be very brief because my review will cover the broad range of topics discussed during this ambitious program. We started by addressing the issue of microbiologic testing, and Dr. Shek recommended standardization by constant improvement, rather than setting up a regulatory-based mechanism to achieve microbiologic testing standards. He gave good reasons for doing this, including the continuing recognition of new agents as well as new methods for diagnosis. Dr. Riley, talking about the standardization of tests, outlined a very exciting program in which they are now engaged in a first phase. This program uses standard specimens to determine the capability or accuracy of individual laboratories and to develop standard operating procedures, which I believe have been needed for a long time. From my perspective, this development is a very positive and important step. Dr. Itoh then discussed factors that cause a lack of uniformity in results. His discussion was based on encounters in the EQUEST monitoring center with discrepancies between several specific agents such as Pasteurella pneumotropica and hemorrhagic fever with renal syndrome. He recommended that in harmonizing the tests, the methods must be enumerated along with the recommendations for their usefulness. Dr. Shibahara described laboratories in Japan, which include 53 national university animal centers plus centers in private universities and municipalities and prefectures. He outlined a concern about international transfer of transgenic and knockout mice, which complicates the worldwide situation considerably. He noted that animals rejected for entry into Japanese laboratories because of infec

OCR for page 143
Microbial Status and Genetic Evaluation of Mice and Rats: PROCEEDINGS OF THE 1999 US/JAPAN CONFERENCE tions they carried have comprised about 8% of both domestic and international introductions. Following these presentations were additional discussions on the desirability of the establishment of recommendations by regulatory organizations, rather than just letting standards evolve over time. Dr. Katiyama pointed out the need to share minimum health profiles and also the importance of requesting reference substances. She compared the agents in the rat serology screens among systems devised by COLASA, Microbiological Associates, and the ICLAS-Asian laboratories in Japan. In the next session, Dr. Smith talked about emerging and reemerging viruses of laboratory rats and mice, including mouse and rat parvoviruses. She also highlighted mouse hepatitis virus, which has existed a long time but continues to recur and has a high prevalence in many mouse colonies including several I have encountered. The effects of many of these agents are extremely important, not only in causing overt disease but also in modifying the immunologic responses. Of course, their effects on genetically modified animals can be expected to be extremely variable as well. Dr. Morse addressed the topic of emerging infections. Using the example of hantaviruses, he pointed out the need to avoid complacency, the need for adequate detection and diagnosis, and the importance of recognizing the role of biodiversity. There are indeed zoonoses that still remain to be identified, and animal models will be essential for studying such infectious disease. He recommended that the group take advantage of information DARPA can provide. Dr. Goto discussed Helicobacter hepaticus detection and elimination using polymerase chain reaction. He also pointed out the most common types of helicobacters, which are important in causing clinical disease in mice in Japan. Dr. Itoh talked about H. hepaticus as a contaminant of tumor tissues that have been passed in mice and also pointed out how to select tests for new infections. He proposed a five-tiered categorization of agents based on pathogenicity, effects on experimental results, convenience of testing, prevalence, and induction of infection. He made a plea for a testing scheme that is not overly extensive. This very briefly summarizes the first nine presentations and related discussions.

Representative terms from entire chapter:

clinical disease