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The origins and uses of mouse outbred stocks


Outbred mouse stocks, often used in genetics, toxicology and pharmacology research, have been generated in rather haphazard ways. Understanding the characteristics of these stocks and their advantages and disadvantages is important for experimental design. In many studies these mice are used inappropriately, wasting animals' lives and resources on suboptimal experiments. Recently, however, researchers from the field of complex trait analysis have capitalized on the genetics of outbred stocks to refine the identification of quantitative trait loci. Here we assess the most widely used outbred stocks of mice and present guidelines for their use.

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Figure 1: Comparison of the response to chloramphenicol in outbred and inbred mice.


  1. 1

    Beck, J.A. et al. Genealogies of mouse inbred strains. Nat. Genet. 24, 23–25 (2000).

    CAS  Article  Google Scholar 

  2. 2

    Festing, M.F.W. International Index of Laboratory Animals 6th edn. (Newbury, England, 1993).

    Google Scholar 

  3. 3

    Festing, M.F. Genetic reliability of commercially-bred laboratory mice. Lab. Anim. 8, 265–270 (1974).

    CAS  Article  Google Scholar 

  4. 4

    Festing, M.F. Genetic monitoring of laboratory mouse colonies in the Medical Research Council Accreditation Scheme for the suppliers of laboratory animals. Lab. Anim. 8, 291–299 (1974).

    CAS  Article  Google Scholar 

  5. 5

    Cui, S., Chesson, C. & Hope, R. Genetic variation within and between strains of outbred Swiss mice. Lab. Anim. 27, 116–123 (1993).

    CAS  Article  Google Scholar 

  6. 6

    Hayakawa, J., Koizumi, T. & Natsuume-Sakai, S. Constancy of genetic variability in mice for non-inbred closed colonies. Lab. Anim. 14, 233–236 (1980).

    CAS  Article  Google Scholar 

  7. 7

    Strivens, M. & Eppig, J.T. Visualizing the laboratory mouse: capturing phenotype information. Genetica 122, 89–97 (2004).

    CAS  Article  Google Scholar 

  8. 8

    Falconer, D.S. Introduction to Quantitative Genetics (Longmans, London, 1981).

    Google Scholar 

  9. 9

    Festing, M., Kondo, K., Loosli, R., Poiley, S.M. & Spiegel, A. International standardized nomenclature for outbred stocks of laboratory animals. Z. Versuchstierkd. 14, 215–224 (1972).

    CAS  PubMed  Google Scholar 

  10. 10

    Festing, M.F. Warning: the use of heterogeneous mice may seriously damage your research. Neurobiol. Aging 20, 237–244 (1999).

    CAS  Article  Google Scholar 

  11. 11

    Holt, M., Nicholas, F.W., James, J.W., Moran, C. & Martin, I.C. Development of a highly fecund inbred strain of mice. Mamm. Genome 15, 951–959 (2004).

    Article  Google Scholar 

  12. 12

    Nomura, T. & Yonezawa, K. A comparison of four systems of group mating for avoiding inbreeding. Genet. Sel. Evol. 28, 141–159 (1996).

    Article  Google Scholar 

  13. 13

    Groen, A. & Lagerwerf, A.J. Genic heterogeneity and genetic monitoring of mouse outbred stocks. Lab. Anim. 13, 81–85 (1979).

    CAS  Article  Google Scholar 

  14. 14

    Katoh, H., Utsu, S., Chen, T.P. & Moriwaki, K. H-2 polymorphisms in outbred strains of mice. Lab. Anim. Sci. 40, 490–494 (1990).

    CAS  PubMed  Google Scholar 

  15. 15

    Kluge, R., Meyer, J. & Rapp, K.G. Genetic characterization of the mouse strains of the Institute for Animal Breeding of the Veterinary Faculty of the University of Munich, Germany. J. Exp. Anim. Sci. 36, 179–188 (1994).

    CAS  PubMed  Google Scholar 

  16. 16

    Rice, M.C. & O'Brien, S.J. Genetic variance of laboratory outbred Swiss mice. Nature 283, 157–161 (1980).

    CAS  Article  Google Scholar 

  17. 17

    Teppner, I., Aigner, B., Schreiner, E., Muller, M. & Windisch, M. Polymorphic microsatellite markers in the outbred CFW and ICR stocks for the generation of speed congenic mice on C57BL/6 background. Lab. Anim. 38, 406–412 (2004).

    CAS  Article  Google Scholar 

  18. 18

    Boucher, W. & Cotterman, C.W. On the classification of regular systems of inbreeding. J. Math. Biol. 28, 293–305 (1990).

    CAS  Article  Google Scholar 

  19. 19

    Caballero, A. & Toro, M.A. Interrelations between effective population size and other pedigree tools for the management of conserved populations. Genet. Res. 75, 331–343 (2000).

    CAS  Article  Google Scholar 

  20. 20

    Petkov, P.M. et al. An efficient SNP system for mouse genome scanning and elucidating strain relationships. Genome Res. 14, 1806–1811 (2004).

    CAS  Article  Google Scholar 

  21. 21

    Russell, R.J., Festing, M.F., Deeny, A.A. & Peters, A.G. DNA fingerprinting for genetic monitoring of inbred laboratory rats and mice. Lab. Anim. Sci. 43, 460–465 (1993).

    CAS  PubMed  Google Scholar 

  22. 22

    Hoger, H. Genetic drift in an outbred stock of mice. Jikken Dobutsu 41, 215–220 (1992).

    CAS  PubMed  Google Scholar 

  23. 23

    Chapin, R.E. et al. Are mouse strains differentially susceptible to the reproductive toxicity of ethylene glycol monomethyl ether? A study of three strains. Fundam. Appl. Toxicol. 21, 8–14 (1993).

    CAS  Article  Google Scholar 

  24. 24

    Poiley, S.M. Growth tables for 66 strains and stocks of laboratory animals. Lab. Anim. Sci. 22, 758–779 (1972).

    CAS  PubMed  Google Scholar 

  25. 25

    Papaioannou, V.E. & Festing, M.F. Genetic drift in a stock of laboratory mice. Lab. Anim. 14, 11–13 (1980).

    CAS  Article  Google Scholar 

  26. 26

    Serfilippi, L.M., Pallman, D.R., Gruebbel, M.M., Kern, T.J. & Spainhour, C.B. Assessment of retinal degeneration in outbred albino mice. Comp. Med. 54, 69–76 (2004).

    CAS  PubMed  Google Scholar 

  27. 27

    Nei, M. Estimation of average heterozygosity and genetic distance from a small number of individuals. Genetics 89, 583–590 (1978).

    CAS  PubMed  PubMed Central  Google Scholar 

  28. 28

    Lynch, C.J. The so-called Swiss mouse. Lab. Anim. Care 19, 214–220 (1969).

    CAS  PubMed  Google Scholar 

  29. 29

    Jay, G.E. Jr. Variation in response of various mouse strains to hexobarbital (evipal). Proc. Soc. Exp. Biol. Med. 90, 378–380 (1955).

    CAS  Article  Google Scholar 

  30. 30

    Dell, R.B., Holleran, S. & Ramakrishnan, R. Sample size determination. ILAR J. 43, 207–213 (2002).

    CAS  Article  Google Scholar 

  31. 31

    Festing, M.F. Principles: the need for better experimental design. Trends Pharmacol. Sci. 24, 341–345 (2003).

    CAS  Article  Google Scholar 

  32. 32

    Felton, R.P. & Gaylor, D.W. Multistrain experiments for screening toxic substances. J. Toxicol. Environ. Health 26, 399–411 (1989).

    CAS  Article  Google Scholar 

  33. 33

    Festing, M.F. & Wolff, G.L. Re: Inbred strains of laboratory animals: superior to outbred mice? J. Natl. Cancer Inst. 87, 1715–1716 (1995).

    CAS  Article  Google Scholar 

  34. 34

    Haseman, J.K. & Hoel, D.G. Statistical design of toxicity assays: role of genetic structure of test animal population. J. Toxicol. Environ. Health 5, 89–101 (1979).

    CAS  Article  Google Scholar 

  35. 35

    Festing, M.F., Diamanti, P. & Turton, J.A. Strain differences in haematological response to chloramphenicol succinate in mice: implications for toxicological research. Food Chem. Toxicol. 39, 375–383 (2001).

    CAS  Article  Google Scholar 

  36. 36

    Flint, J., Valdar, W., Shifman, S. & Mott, R. Strategies for mapping and cloning quantitative trait genes in rodents. Nat. Rev. Genet. 6, 271–286 (2005).

    CAS  Article  Google Scholar 

  37. 37

    Hitzemann, R. et al. Multiple cross mapping (MCM) markedly improves the localization of a QTL for ethanol-induced activation. Genes Brain Behav. 1, 214–222 (2002).

    CAS  Article  Google Scholar 

  38. 38

    Manenti, G., Galbiati, F., Noci, S. & Dragani, T.A. Outbred CD-1 mice carry the susceptibility allele at the pulmonary adenoma susceptibility 1 (Pas1) locus. Carcinogenesis 24, 1143–1148 (2003).

    CAS  Article  Google Scholar 

  39. 39

    Mott, R., Talbot, C.J., Turri, M.G., Collins, A.C. & Flint, J. A method for fine mapping quantitative trait loci in outbred animal stocks. Proc. Natl. Acad. Sci. USA 97, 12649–12654 (2000).

    Article  Google Scholar 

  40. 40

    Talbot, C.J. et al. High-resolution mapping of quantitative trait loci in outbred mice. Nat. Genet. 21, 305–308 (1999).

    CAS  Article  Google Scholar 

  41. 41

    Talbot, C. J. et al. Fine scale mapping of a genetic locus for conditioned fear. Mamm. Genome 14, 223–230 (2003).

    Article  Google Scholar 

  42. 42

    Yalcin, B. et al. Genetic dissection of a behavioral quantitative trait locus shows that Rgs2 modulates anxiety in mice. Nat. Genet. 36, 1197–1202 (2004).

    CAS  Article  Google Scholar 

  43. 43

    Demarest, K., Koyner, J., McCaughran, J. Jr., Cipp, L. & Hitzemann, R. Further characterization and high-resolution mapping of quantitative trait loci for ethanol-induced locomotor activity. Behav. Genet. 31, 79–91 (2001).

    CAS  Article  Google Scholar 

  44. 44

    McClearn, G.E., Wilson, J.R. & Meredith, W. Contributions to Behaviour-Genetic Analysis: The Mouse as a Prototype 3–22 (Appleton Centry Crofts, New York, 2005).

    Google Scholar 

  45. 45

    Padeh, B., Wahlsten, D. & DeFries, J.C. Operant discrimination learning and operant bar-pressing rates in inbred and heterogeneous laboratory mice. Behav. Genet. 4, 383–393 (1974).

    CAS  Article  Google Scholar 

  46. 46

    DeFries, J.C., Wilson, J.R., Erwin, V.G. & Petersen, D.R.L.S.X. SS recombinant inbred strains of mice: initial characterization. Alcohol. Clin. Exp. Res. 13, 196–200 (1989).

    CAS  Article  Google Scholar 

  47. 47

    Feingold, N. et al. Polygenic regulation of antibody synthesis to sheep erythrocytes in the mouse: a genetic analysis. Eur. J. Immunol. 6, 43–51 (1976).

    CAS  Article  Google Scholar 

  48. 48

    Schlager, G. Genetic Hypertension in the Mouse 158–172 (Elsevier, Amsterdam, 1994).

    Google Scholar 

  49. 49

    Boutwell, R.K. Some biological aspects of skin carcinogenesis. Prog. Exp. Tumor Res. 19, 207–250 (1964).

    Google Scholar 

  50. 50

    Mathews, C.E., Bagley, R. & Leiter, E.H. ALS/Lt: a new type 2 diabetes mouse model associated with low free radical scavenging potential. Diabetes 53 Suppl 1, S125–S129 (2004).

    CAS  Article  Google Scholar 

  51. 51

    Garland, T., Jr et al. Evolution of a small-muscle polymorphism in lines of house mice selected for high activity levels. Evolution Int. J. Org. Evolution 56, 1267–1275 (2002).

    Article  Google Scholar 

  52. 52

    Kirkpatrick, B.W., Mengelt, A., Schulman, N. & Martin, I.C. Identification of quantitative trait loci for prolificacy and growth in mice. Mamm. Genome 9, 97–102 (1998).

    CAS  Article  Google Scholar 

  53. 53

    Horvat, S. et al. Mapping of obesity QTLs in a cross between mouse lines divergently selected on fat content. Mamm. Genome 11, 2–7 (2000).

    CAS  Article  Google Scholar 

  54. 54

    Crabbe, J.C., Belknap, J.K. & Buck, K.J. Genetic animal models of alcohol and drug abuse. Science 264, 1715–1723 (1994).

    CAS  Article  Google Scholar 

  55. 55

    Grahame, N.J., Li, T.K. & Lumeng, L. Selective breeding for high and low alcohol preference in mice. Behav. Genet. 29, 47–57 (1999).

    CAS  Article  Google Scholar 

  56. 56

    Tabakoff, B., Bhave, S.V. & Hoffman, P.L. Selective breeding, quantitative trait locus analysis, and gene arrays identify candidate genes for complex drug-related behaviors. J. Neurosci. 23, 4491–4498 (2003).

    CAS  Article  Google Scholar 

  57. 57

    Biozzi, G. et al. Genetic analysis of antibody responsiveness to sheep erythrocytes in crosses between lines of mice selected for high or low antibody synthesis. Immunology 36, 427–438 (1979).

    CAS  PubMed  PubMed Central  Google Scholar 

  58. 58

    Baker, D. et al. Induction of chronic relapsing experimental allergic encephalomyelitis in Biozzi mice. J. Neuroimmunol. 28, 261–270 (1990).

    CAS  Article  Google Scholar 

  59. 59

    Tinston, D.J., Chart, I.S., Godley, M.J., Gore, C.W.G.B.A. & Litchfield, M.H. Chlorodifluoromethane (CFC 22): Long Term Inhalation Study in the Mouse. Report No. CTL/P/547. (Imperial Chemical Industries Limited, Central Toxicology Laboratory, Alderley Park, Cheshire, UK, 1981).

    Google Scholar 

  60. 60

    Anghileri, L.J., Mayayo, E., Domingo, J.L. & Thouvenot, P. Radiofrequency-induced carcinogenesis: cellular calcium homeostasis changes as a triggering factor. Int. J. Radiat. Biol. 81, 205–209 (2005).

    CAS  Article  Google Scholar 

  61. 61

    Hauschka, T. S. & Mirand, E. A. Perspectives in Cancer Research and Treatment vol. 25, 319 (Roswell Park Memorial Institute, New York, 1973).

    Google Scholar 

  62. 62

    Nobunaga, T. Establishment by selective inbreeding of the IVCS strain and related sister strains of the mouse, demonstrating regularly repeated 4-day estrous cycles. Lab. Anim. Sci. 23, 803–811 (1973).

    CAS  PubMed  Google Scholar 

  63. 63

    Darvasi, A. Dissecting complex traits: the geneticists' “Around the world in 80 days.” Trends Genet. 21, 373–376 (2005).

    CAS  Article  Google Scholar 

  64. 64

    Stahl, W., Sekiguchi, M. & Kaneda, Y. Cerebellar anomalies in congenital murine toxoplasmosis. Parasitol. Res. 88, 507–512 (2002).

    CAS  Article  Google Scholar 

  65. 65

    Benson, L.M. & Abelseth, M.K. Investigation of the histocompatibility of the NYA:NYLAR mouse colony by skin grafting. Lab. Anim. Sci. 27, 333–335 (1977).

    CAS  PubMed  Google Scholar 

  66. 66

    DiGiovanni, J. Genetic factors controlling responsiveness to skin tumor promotion in mice. Prog. Clin. Biol. Res. 391, 195–212 (1995).

    CAS  PubMed  Google Scholar 

  67. 67

    Hennings, H., Lowry, D.T., Yuspa, S.H., Mock, B. & Potter, M. New strains of inbred SENCAR mice with increased susceptibility to induction of papillomas and squamous cell carcinomas in skin. Mol. Carcinog. 20, 143–150 (1997).

    CAS  Article  Google Scholar 

  68. 68

    Ku, S.K., Lee, J.H., Lee, H.S. & Park, K.D. The regional distribution and relative frequency of gastrointestinal endocrine cells in SHK-1 hairless mice: an immunohistochemical study. Anat. Histol. Embryol. 31, 78–84 (2002).

    Article  Google Scholar 

  69. 69

    Hornady, M.H. Changes in the testicular and preputial gland structures of mice related to influence of Ferula hormonis extrtact. Sciences (New York) 1, 108–112 (2001).

    Google Scholar 

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We thank R.D. Mastrocco for information about Clara Lynch; J. Eppig, R. Hitzemann, H. Jacob, M. Josten, R. Kalman, I. Martin, G. McClearn, R. Mott, J. Stitzel and R. Williams for personal communications; R. Young for graphics; and the Brain Research Trust and the Motor Neuron Disease Association for funding.

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Correspondence to Elizabeth M C Fisher.

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M.F.W.F. has a consultancy with Harlan Limited.

Supplementary information

Supplementary Fig. 1

Genealogy of major Swiss mice outbred stocks. (PDF 181 kb)

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Chia, R., Achilli, F., Festing, M. et al. The origins and uses of mouse outbred stocks. Nat Genet 37, 1181–1186 (2005).

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