Mouse Breeding and Colony Management

Abdelkader Ayadi1, Gisèle Ferrand2, Isabelle Goncalves da Cruz1, Xavier Warot2

1 Institut Clinique de la Souris (ICS), Illkirch, France, 2 Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland
Publication Name:  Current Protocols in Mouse Biology
Unit Number:   
DOI:  10.1002/9780470942390.mo100214
Online Posting Date:  March, 2011
GO TO THE FULL TEXT: PDF or HTML at Wiley Online Library


The possibility to genetically modify the mouse genome has enabled the creation of numerous lines of genetically engineered mouse models (GEMMs). As a result, the demand for housing space in research facilities is increasing. Knowledge of the basis of mouse reproduction and of the methods to handle colonies of GEMMs is therefore mandatory to efficiently populate facilities. The mouse has a short generation period, produces large progenies, and can breed all year round. However, environmental parameters (bedding, diet, cage type, temperature, hygrometry, light, noise, and sanitary status) strongly influence the breeding efficiency and experimental data, and must be tightly controlled. Efficient GEMM colony management requires adequate recording of breeding and proper identification and genotyping of animals. Various mating types and breeding schemes can be used, depending on the type of studies conducted. The recent development of assisted reproduction methods helps circumvent some of the issues faced with those lines especially difficult to breed. Curr. Protoc. Mouse Biol. 1:239‐264. © 2011 by John Wiley & Sons, Inc.

Keywords: mouse; reproduction; breeding; efficiency; mating; colony management; assisted reproduction

PDF or HTML at Wiley Online Library

Table of Contents

  • Introduction
  • Basics of Mouse Reproduction
  • Factors Affecting Breeding Efficiency: Environmental Parameters
  • Factors Affecting Breeding Efficiency: Sanitary Status
  • Colony Management
  • Specific Breeding Methods: Assisted Reproduction Techniques
  • Conclusion
  • Acknowledgements
  • Literature Cited
  • Figures
  • Tables
PDF or HTML at Wiley Online Library


PDF or HTML at Wiley Online Library



Literature Cited

   Auerbach, W., Dunmore, J., Fairchild‐Huntress, V., Fang, Q., Auerbach, A., Huszar, D., and Joyner, A. 2000. Establishment and chimera analysis of 129/SvEv‐ and C57BL/6‐derived mouse embryonic stem cell lines. Biotechniques 29:1024‐1032.
   Auerbach, A., Norinsky, R., Ho, W., Losos, K., Guo, Q., Chatterjee, S., and Joyner, A. 2003. Strain‐dependent differences in the efficiency of transgenic mouse production. Transgenic. Res. 12:59‐69.
   Birling, M.C., Gofflot, F., and Warot, X. 2009. Site‐specific recombinases for manipulation of the mouse genome. In Transgenesis Techniques, Methods in Molecular Biology ( E.J. Cartwright, ed.) pp. 245‐263. Humana Press, Totowa, New Jersey.
   BVAAWF/FRAME/RSPCA/UFAW, Joint Working Group on Refinement. 2003. Refinement and reduction in production of genetically modified mice. Lab. Anim. 37:S1‐S49.
   Castelhano‐Carlos, M.J. and Baumans, V. 2010. Noise and light in the vivarium. ALN World 3:12‐17.
   Castelhano‐Carlos, M., Sousa, N., Ohl, F., and Baumans, V. 2010. Identification methods in newborn C57BL/6 mice: A developmental and behavioural evaluation. Lab. Anim. 44:88‐103.
   Champlin, A., Dorr, D., and Gates, A. 1973. Determining the stage of the estrous cycle in the mouse by the appearance of the vagina. Biol. Reprod. 8:491‐494.
   Crusio, W., Goldowitz, D., Holmes, A., and Wolfer, D. 2009. Standards for the publication of mouse mutant studies. Genes Brain Behav. 8:1‐4.
   Davisson, M.T. and Linder, C.L. 2004. Historical foundations. In The Laboratory Mouse (H.J. Hedrich and G. Bullock, eds.) pp. 15‐24. Elsevier Academic Press, Boston, Massachusetts.
   Doetschman, T. 2009. Influence of genetic background on genetically engineered mouse phenotypes. Methods Mol. Biol. 530:423‐433.
   Donnelly, C., McFarland, M., Ames, A., Sundberg, B., Springer, D., Blauth, P., and Bult, C. 2010. JAX Colony Management System (JCMS): An extensible colony and phenotype data management system. Mamm. Genome 21:205‐215.
   Festing, M.F.W. and Peters, A.G. 1999. Animal production and breeding methods. In The UFAW Handbook on the Care and Management of Laboratory Animals, Vol. 1, 7th ed. (T. Poole, ed.) pp. 28‐44. Blackwell Science Ltd, Oxford.
   Gofflot, F., Wendling, O., Chartoire, N., Birling, M.C., Warot, X., and Auwerx, J. 2011. Characterization and validation of Cre‐driver mouse lines. Curr. Protoc. Mouse Biol. 1:1‐15.
   Guénet, J‐L. and Benavides, F.J. 2011. Mouse strains and genetic nomenclature. Curr. Protoc. Mouse Biol. 1:213‐238.
   Hagn, M., Marschall, S., and Hrabé de Angelis, M. 2007. EMMA‐the European mouse mutant archive. Brief Funct. Genomic Proteomic 6:186‐192.
   Hardy, P. 2004. Gnotobiology and breeding techniques. In The Laboratory Mouse (H.J. Hedrich and G. Bullock, eds.) pp. 409‐433. Elsevier Academic Press, Boston, Massachusetts.
   Havenaar, R., Meijer, J.C., Morton, D.B., Ritskes‐Hoitinga, J., and Zwart, P. 1993. Biology and husbandry of laboratory animals. In Principles of Laboratory Animal Science (L.F.M. van Zutphen, V. Baumans and A.C. Beynene, eds.) pp. 17‐74. Elsevier Science Publishers, Maarssen, Netherlands.
   The International Mouse Knockout Consortium. 2007. A mouse for all reasons. Cell 128:9‐13.
   The Jackson Laboratory. 2009. Breeding Strategies for Maintaining Colonies of Laboratory Mice Manual. Available online at:
   Kawase, Y., Iwata, T., Toyoda, Y., Wakayama, T., Yanagimachi, R., and Suzuki, H. 2001. Comparison of intracytoplasmic sperm injection for inbred and hybrid mice. Mol. Reprod. Dev. 60:74‐78.
   Keskintepe, L., Norris, K., Pacholczyk, G., Dederscheck, S., and Eroglu, A. 2007. Derivation and comparison of C57BL/6 embryonic stem cells to a widely used 129 embryonic stem cell line. Transgenic Res. 16:751‐758.
   Landel, C. 2010. Cryopreservation of mouse gametes and embryos. Methods Enzymol. 476:85‐105.
   Le Calvez, S., Perron‐Lepage, M., and Burnett, R. 2006. Subcutaneous microchip‐associated tumours in B6C3F1 mice: A retrospective study to attempt to determine their histogenesis. Exp. Toxicol. Pathol. 57:255‐265.
   Lee, S. and van der Boot, L.M. 1955. Spontaneous pseudopregnancy in mice. Acta Physiol. Pharmacol. Neerl. 4:442‐443.
   Lemken, B. 2010. Rethinking global water quality standards. ALN World 3:12‐16.
   Markel, P., Shu, P., Ebeling, C., Carlson, G., Nagle, D., Smutko, J., and Moore, K. 1997. Theoretical and empirical issues for marker‐assisted breeding of congenic mouse strains. Nat. Genet. 17:280‐284.
   Matzuk, M. and Lamb, D. 2008. The biology of infertility: Research advances and clinical challenges. Nat. Med. 14:1197‐1213.
   Montoliu, L. and Whitelaw, C. 2010. Using standard nomenclature to adequately name transgenes, knockout gene alleles and any mutation associated to a genetically modified mouse strain. Transgenic Res. 19:587‐594.
   Mouse Genome Sequencing Consortium. 2002. Initial sequencing and comparative analysis of the mouse genome. Nature 420:520‐562.
   Nagy, A., Gertsenstein, M., Vintersten, K., and Behringer, R. 2003. Manipulating the mouse embryo. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York.
   National Research Council. 1991. Infectious diseases of mice and rats. Committee on infectious diseases in mice and rats. Institute of Laboratory Animal Resources, Commission of Life Sciences. National Academies Press, Washington D.C.
   National Research Council, 2010. Guide for the Care and Use of Laboratory Animals. National Academies Press, Washington D.C.
   Naz, R., Engle, A., and None, R. 2009. Gene knockouts that affect male fertility: Novel targets for contraception. Front. Biosci. 14:3994‐4007.
   Nicklas, W., Baneux, P., Boot, R., Decelle, T., Deeny, A.A., Fumanelli, M., and Illgen‐Wilcke, B. 2002. Recommendations for the health monitoring of rodent and rabbit colonies in breeding and experimental units. Lab. Anim. 36:20‐42.
   Ogonuki, N., Inoue, K., Hirose, M., Miura, I., Mochida, K., Sato, T., Mise, N., Mekada, K., Yoshiki, A., Abe, K., Kurihara, H., Wakana, S., and Ogura, A. 2009. A high‐speed congenic strategy using first‐wave male germ cells. PLoS One 4:e4943.
   Ostermeier, G., Wiles, M., Farley, J., and Taft, R. 2008. Conserving, distributing and managing genetically modified mouse lines by sperm cryopreservation. PLoS One 3:e2792.
   Pettitt, S, Liang, Q., Rairdan, X., Moran, J., Prosser, H., Beier, D., Lloyd, K., Bradley, A., and Skarnes, W. 2009. Agouti C57BL/6N embryonic stem cells for mouse genetic resources. Nat. Methods 6:493‐495.
   Rülicke, T., Montagutelli, X., Pintado, B., Thon, R., Hedrich, H., and Group, F.W. 2007. FELASA guidelines for the production and nomenclature of transgenic rodents. Lab. Anim. 41:301‐311.
   Russell, W. and Burch, R. 1959. The Principle of Humane Experimental Technique. Metheun & Co. Ltd, London.
   Schaefer, D., Asner, I., Seifert, B., Bürki, K., and Cinelli, P. 2010. Analysis of physiological and behavioural parameters in mice after toe clipping as newborns. Lab. Anim. 44:7‐13.
   Silver, L. 1995. Mouse Genetics: Concepts and Applications. Oxford University Press, New York.
   Smith, E., Stockwell, J.D., Schweitzer, I., Langley, S.H., and Smith, A.L. 2004. Evaluation of cage micro‐environment of mice housed on various types of bedding materials. Contemp. Top. Lab. Anim. Sci. 43:12‐17.
   Szczygiel, M., Kusakabe, H., Yanagimachi, R., and Whittingham, D. 2002. Intracytoplasmic sperm injection is more efficient than in vitro fertilization for generating mouse embryos from cryopreserved spermatozoa. Biol. Reprod. 67:1278‐1284.
   Sztein, J., Sweet, H., Farley, J., and Mobraaten, L. 1998. Cryopreservation and orthotopic transplantation of mouse ovaries: New approach in gamete banking. Biol. Reprod. 58:1071‐1074.
   Sztein, J., Farley, J., and Mobraaten, L. 2000. In vitro fertilization with cryopreserved inbred mouse sperm. Biol. Reprod. 63:1774‐1780.
   van Gassen, K., Hessel, E., Ramakers, G., Notenboom, R., Wolterink‐Donselaar, I., Brakkee, J., Godschalk, T., Qiao, X., Spruijt, B., van Nieuwenhuizen, O., and de Graan, P. 2008. Characterization of febrile seizures and febrile seizure susceptibility in mouse inbred strains. Genes Brain Behav. 7:578‐586.
   Voipio, H.‐M., Tsai, P.‐P., Brandstetter, H., Gyger, M., Hackbarth, H., Kornerup Hansen, A., and Krohn, T. 2010. Housing and care of laboratory animals. In The COST Manual of Laboratory Animal Care and Use, Refinement, Reduction, and Research (B. Howard, T. Nevalainen, and G. Perretta, eds.) pp. 29‐73. CRC Press, Boca Raton, Fla.
   Wakeland, E., Morel, L., Achey, K., Yui, M., and Longmate, J. 1997. Speed congenics: A classic technique in the fast lane (relatively speaking). Immunol. Today 18:472‐477.
   White, W.J. 2007. Management and design: Breeding facilities. In The Mouse in Biomedical Research (J.G. Fox ed.) pp. 235‐270. Academic Press, Amsterdam.
   Whitten, W.K. 1959. Occurrence of anoestrus in mice caged in groups. J. Endocrinol. 18:102‐107.
   Wilkinson, P., Sengerova, J., Matteoni, R., Chen, C., Soulat, G., Ureta‐Vidal, A., Fessele, S., Hagn, M., Massimi, M., Pickford, K., Butler, R., Marschall, S., Mallon, A., Pickard, A., Raspa, M., Scavizzi, F., Fray, M., Larrigaldie, V., Leyritz, J., Birney, E., Tocchini‐Valentini, G., Brown, S., Herault, Y., Montoliu, L., Hrabé de Angelis, M., and Smedley, D. 2010. EMMA‐mouse mutant resources for the international scientific community. Nucleic Acids Res. 38:D570‐D576.
   Wolfer, D., Crusio, W., and Lipp, H. 2002. Knockout mice: Simple solutions to the problems of genetic background and flanking genes. Trends Neurosci. 25:336‐340.
   Wooten, R.M., Ma, Y., Yoder, R.A., Brown, J.P., Wies, J.H., Zachary, J.F., Kirschning, C.J., and Weis, J.J. 2002. Toll‐like receptor 2 is required for innate, but not acquired, host defense to Borrelia burgdorferi. J. Immunol. 168:348‐355.
Internet Ressources
  Web site of the Jackson Laboratory. A number of online useful resources on mouse reproduction freely available (books, manuals, posters).
PDF or HTML at Wiley Online Library