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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
144
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Microbial Status and Genetic Evaluation of Mice and Rats: PROCEEDINGS OF THE 1999 US/JAPAN CONFERENCE

Concluding Comments

John Vandenbergh

North Carolina State University

Raleigh, NC

I would like to share a number of recommendations that I heard without associating them with particular speakers. Many of the speakers presented very specific recommendations, which in some cases were new to me and probably were new to others.

One important discussion centered on the maintenance of genetic diversity in outbred stocks, avoiding drift and the various bottlenecks that can appear. We used terms such as rotation, or migration among colonies that are scattered about, and the technique of making crosses (such as four-way crosses).

We heard that colleagues in toxicology have not been taking advantage of information resulting from genetic analysis. I agree with that premise and refer to a recently published paper (Spearow and others 1999) showing that the strain of mice most frequently used by toxicologists, the CD1 strain, is also the least responsive to estrogen among all strains that have been tested. Yet, so much of environmental estrogen is now being tested on that particular strain of mouse. I believe it is necessary to reexamine that testing. One other suggestion that I believe requires additional thought is that of developing one or more global strains.

We learned that we can use the team approach to phenotyping. In addition, I think we can use simple but elegant behavioral assays that are available and have been described in some detail. It may be advisable to use genetically altered mice or rats as strains that can be used over a long time, rather than use only the selected strains we have. Finally, near the end of our discussion, the fascinating term dramatype was explained.

In closing and on behalf of the International Committee of the Council of the Institute for Laboratory Animal Research (ILAR), I want to thank all the speakers and Ralph Dell and the ILAR staff for hosting an excellent meeting. The Na

Page
144
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 144
Microbial Status and Genetic Evaluation of Mice and Rats: PROCEEDINGS OF THE 1999 US/JAPAN CONFERENCE Concluding Comments John Vandenbergh North Carolina State University Raleigh, NC I would like to share a number of recommendations that I heard without associating them with particular speakers. Many of the speakers presented very specific recommendations, which in some cases were new to me and probably were new to others. One important discussion centered on the maintenance of genetic diversity in outbred stocks, avoiding drift and the various bottlenecks that can appear. We used terms such as rotation, or migration among colonies that are scattered about, and the technique of making crosses (such as four-way crosses). We heard that colleagues in toxicology have not been taking advantage of information resulting from genetic analysis. I agree with that premise and refer to a recently published paper (Spearow and others 1999) showing that the strain of mice most frequently used by toxicologists, the CD1 strain, is also the least responsive to estrogen among all strains that have been tested. Yet, so much of environmental estrogen is now being tested on that particular strain of mouse. I believe it is necessary to reexamine that testing. One other suggestion that I believe requires additional thought is that of developing one or more global strains. We learned that we can use the team approach to phenotyping. In addition, I think we can use simple but elegant behavioral assays that are available and have been described in some detail. It may be advisable to use genetically altered mice or rats as strains that can be used over a long time, rather than use only the selected strains we have. Finally, near the end of our discussion, the fascinating term dramatype was explained. In closing and on behalf of the International Committee of the Council of the Institute for Laboratory Animal Research (ILAR), I want to thank all the speakers and Ralph Dell and the ILAR staff for hosting an excellent meeting. The Na

OCR for page 145
Microbial Status and Genetic Evaluation of Mice and Rats: PROCEEDINGS OF THE 1999 US/JAPAN CONFERENCE tional Center for Research Resources of the National Institutes of Health has been very generous in providing some support for this program in addition to the Central Institute in Japan and the Japanese government. Finally, I thank Dr. Nomura who, with Dr. Held, started all of these discussions in the 1980s and who has been the driving force behind this meeting as well as the subject of normalization of animal use. Their good start and continued pressure in the area has made possible the success of this meeting. REFERENCE Spearow, J.L., P. Doemeny, R. Sera, R. Leffler, and M. Barkley. 1999. Genetic variation in susceptibility to endocrine disruption by estrogen in mice. Science 285:1259-1261.

OCR for page 146
Microbial Status and Genetic Evaluation of Mice and Rats: PROCEEDINGS OF THE 1999 US/JAPAN CONFERENCE This page in the original is blank.

Representative terms from entire chapter:

selected strains