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
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Abstract

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

     
 
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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
     
 
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Materials

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Figures

  •   FigureFigure 1. Health monitoring in accordance with FELASA recommendations (adapted from Nicklas et al., ).
  •   FigureFigure 2. Common terminology for microbiological status of laboratory rodents (adapted from National Research Council, ).
  •   FigureFigure 3. Example of a cage card with breeding records and of a colony log to manage a GEMM mouse colony. (A) Important information such as line name, owner of the line, animal ID, gender, date of birth, genotype, and parentage should be indicated on the breeding card. For an efficient breeding program, breeding set‐up and retirement dates should be known. (B) A separate mouse colony log with the data of all animals of the colony (animals used for breeding, experimentation, and stock) is necessary to manage the colony in an effective and safe way.
  •   FigureFigure 4. Ear notching in mice. Example of a numbering system for identifying mice. The scheme represents the dorsal view of the head of a mouse, with the position of notches within the ear. Units correspond to notches in the right ear, tens to notches in the left ear. Numbers 5 to 9 and 50 to 90 are created by a combination of two notches, as indicated. By combining notches for units and tens, one is able to number animals starting at 1 up to 99.
  •   FigureFigure 5. Complex breeding strategy: generation of a conditional, tissue‐specific, gene knock‐out in mice through a classical Cre‐loxP strategy. The floxed mouse is obtained by introducing loxP sites around an essential exon of the gene of interest and using classical homologous recombination in ES cells. The Cre‐expressing mouse, in which the Cre recombinase is under the control of a tissue‐specific promoter (TSP), is usually a transgenic line produced by pronuclear microinjection. Both lines are established and maintained independently, the floxed line at the homozygous stage and the Cre line at the hemizygous stage. In a first step, the Cre line and the floxed homozygous line are intercrossed. Fifty percent of the offspring harbor the Cre transgene (highlighted in light orange on the figure) and a floxed allele of the gene of interest. Those animals are then once again crossed with the floxed homozygous line resulting in 25% of the offspring being homozygous for the floxed gene and hemizygous for the Cre. In those animals, excision of the floxed exon occurs only in Cre‐expressing cells or tissue, while the gene of interest remains functional in other cells (highlighted in light blue on the figure). Such two‐step breeding strategies allows the generation of experimental (Cre hemizygous, floxed gene homozygous) and appropriate control (floxed gene homozygous) animals at the same time with an intermediate frequency. Numbers correspond to the theoretical percentage of animals of a given genotype.
  •   FigureFigure 6. Sizing a mouse colony appropriately: Two case studies showing how to calculate the number of breeding cages required for a GEMM colony. Calculations are based on the colony characteristics and reproductive performance, number of animals, age, genotype, and gender required (adapted from The Jackson Laboratory, ).
  •   FigureFigure 7. Backcross breeding scheme to generate a congenic GEMM. In this example, a targeted mutation (Gene tm) is generated from 129S2/SvPas ES cells (genetic background represented here by a brown circle). To transfer the mutation onto the recipient C57BL/6J background (represented here by a black circle), a germline competent chimera (i.e., heterozygote carrier for a targeted mutation Gene tm/+) is first crossed with the inbred C57BL/6J strain (outcross). The F1 progeny is screened for the mutation: 50% of the genome of the F1 offspring comes from the 129S2/SvPas strain and 50% from the C57BL/6J strain (depicted by brown and black hemispheres in the circle). Then, F1 heterozygous Gene tm/+ are backcrossed to C57BL/6J. Heterozygous progeny of the F1 and subsequent generations are backcrossed to C57BL/6J until the tenth generation. N10 offspring are considered congenic, i.e., genetically identical to the C57BL/6J inbred strain except for the targeted gene locus and its surrounding region (represented here by the residual brown area within the black circle of N10).

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Internet Ressources
  http://www.jax.org
  Web site of the Jackson Laboratory. A number of online useful resources on mouse reproduction freely available (books, manuals, posters).
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