Mouse Genetics as a Research Tool


Mouse genetics elaborates on the genetic variation between genetically homogeneous inbred strains. Because the genetic variation can be controlled, crosses between such inbred strains allow unraveling of the genetic basis of multigenic disorders such as cancer and atherosclerosis.

Keywords: genetic mapping; quantitative trait locus; inbred strain

Figure 1.

F1 hybrids. Offspring result from an outcross between two inbred strains (first filial generation). Their genome is heterozygous (50% genome from strain A and 50% from strain B) and all siblings are identical to each other.

Figure 2.

Backcross. A mating between a heterozygous F1 animal and one of the parental homozygous strains. All individuals are genetically different and contain 25% of their genome from strain A and 75% from strain B. At any single locus, approximately 50% will be heterozygous (AB) and 50% homozygous (BB).

Figure 3.

F2 intercross. A mating set up between brothers and sisters from the F1 generation or between any other two mice that are identically heterozygous at a particular locus. The offspring from an F2 cross are genetically different and distributed among three genotypes at any single locus: 25% will be homozygous AA, 50% heterozygous AB and 25% homozygous BB.

Figure 4.

Congenic strain. Recombinants between two inbred strains are backcrossed to produce a strain that carries a single chromosomal region from one strain on the genetic background of the other strain.

Figure 5.

Recombinant inbred stains (RIS) are produced by sequential generations of brother–sister mating between animals of an F2 generation of a cross between two inbred strains. From brother–sister mating of randomly selected pairs of F2 mice, multiple independent strains are established without selection.

Figure 6.

Construction of BcA recombinant congenic strains from the donor strain A and background strain B. Twenty generations or more of brother–sister mating of different pairs of second backcross (N3) mice, each pair derived from a different N2 mouse. Each BcA strain has inherited 12.5% of the genes from strain A and 87% from strain B.

Figure 7.

Construction of a chromosome substitution strain (CSS) from the donor strain A and the background strain B (CSS B.A). Progeny with a nonrecombinant chromosome (e.g. chromosome 2, Chr 2) from donor strain A are identified in the N2 and subsequent backcrosses. At N11, males and females with the nonrecombinant chromosome are intercrossed. The offspring that are homozygous for chromosome 2 are used to propagate the homozygous CSS B.A‐Chr2 strain.



Beck JA, Lloyd S, Hafezparast M, et al. (2000) Genealogies of mouse inbred strains. Nature Genetics 24(1): 23–25.

Broman KW (2001) Review of statistical methods for QTL mapping in experimental crosses. Laboratory Animals 30(7): 44–52.

Campino S, Behrschmidt C, Bagot S, et al. (2002) Unique genetic variation revealed by a microsatellite polymorphism survey in ten wild‐derived inbred strains. Genomics 79(5): 618–620.

Dansky HM, Shu P, Donavan M, et al. (2002) A phenotype‐sensitizing Apoe‐deficient genetic background reveals novel atherosclerosis predisposition loci in the mouse. Genetics 160(4): 1599–1608.

Doerge RW (2002) Mapping and analysis of quantitative trait loci in experimental populations. Nature Reviews Genetics 3(1): 43–52.

Lander E and Kruglyak L (1995) Genetic dissection of complex traits: guidelines for interpreting and reporting linkage results. Nature Genetics 11(3): 241–247.

Manly KF and Olson JM (1999) Overview of QTL mapping software and introduction to map manager QT. Mammalian Genome: Official Journal of the International Mammalian Genome Society 10(4): 327–334.

Markel P, Shu P, Ebeling C, et al. (1997) Theoretical and empirical issues for marker‐assisted breeding of congenic mouse strains. Nature Genetics 17(3): 280–284.

Matin A and Nadeau JH (2001) Sensitized polygenic trait analysis. Trends in Genetics 17(12): 727–731.

Nadeau JH, Singer JB, Matin A and Lander ES (2000) Analyzing complex genetic traits with chromosome substitution strains. Nature Genetics 24(3): 221–225.

Shalom A and Darvasi A (2002) Experimental designs for QTL fine mapping in rodents. Methods in Molecular Biology 195: 199–223.

Wakeland E, Morel L, Achey K, Yui M and Longmate J (1997) Speed congenics: a classic technique in the fast lane (relatively speaking). Immunology Today 18(10): 472–477.

van Wezel T, Lipoldova M and Demant P (2001) Identification of disease susceptibility genes (modifiers) in mouse models: cancer and infectious diseases. In: Malcolm S and Goodship J (eds.) Genotype to Phenotype, chap. 7, pp. 107–129. Oxford, UK: BIOS Scientific.

Williams RW, Gu J, Qi S and Lu L (2001) The genetic structure of recombinant inbred mice: high‐resolution consensus maps for complex trait analysis. Genome Biology 2(11) 46.1–46.18.

Further Reading

Avner P, Bruls T, Poras I, et al. (2001) A radiation hybrid transcript map of the mouse genome. Nature Genetics 29(2): 194–200.

Copeland NG, Jenkins NA and Court DL (2001) Recombineering: a powerful new tool for mouse functional genomics. Nature Reviews Genetics 2: 769–779.

Denny P and Justice M (2000) Mouse as the measure of man. Trends in Genetics 16(7): 283–287.

Gregory SG, et al. (2002) A physical map of the mouse genome. Nature 418: 743–750.

Hudson TJ, Church DM and Greenaway S, et al. (2001) A radiation hybrid map of mouse genes. Nature Genetics 29(2): 201–205.

Justice M (2000) Capitalizing on large‐scale mouse mutagenesis screens. Nature Reviews Genetics 1: 109–115.

Lyon MF (2002) A personal history of the mouse genome. Annual Review of Genomics and Human Genetics 3: 1–16.

Nadeau JH (2001) Modifier genes in mice and humans. Nature Reviews Genetics 2(3): 165–171.

Okazaki Y, Furuno M, Kasukawa T, et al. (2002) Analysis of the mouse transcriptome based on functional annotation of 60,770 full‐length cDNAs. Nature 429: 563–573.

Rossant J and McKerlie C (2001) Mouse‐based phenogenomics for modeling human disease. Trends in Molecular Medicine 7(11): 502–507.

Wade CM, Kulbokas III EJ, Kirby AW, et al. (2002) The mosaic structure of variation in the laboratory mouse genome. Nature 420: 574–578.

Waterston RH, Lindblad‐Toh K, Birney E, et al. (2002) Initial sequencing and comparative analysis of the mouse genome. Nature 420: 520–562.

Yu Y and Bradley A (2001) Engineering chromosomal rearrangements in mice. Nature Reviews Genetics 2: 780–790.

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Moen, Corina, and Hofker, Marten(Jan 2006) Mouse Genetics as a Research Tool. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1038/npg.els.0005681]