Mouse Genetics as a Research Tool

Corina Moen, Leiden University Medical Center, Leiden, The Netherlands
Marten Hofker, University of Maastricht, Maastricht, The Netherlands

Published online: January 2006

DOI: 10.1038/npg.els.0005681

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.
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    Wade CM, Kulbokas III EJ, Kirby AW, et al. (2002) The mosaic structure of variation in the laboratory mouse genome. Nature 420: 574–578.
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Article Title: Mouse Genetics as a Research Tool
 
How to Cite close
Moen, Corina, and Hofker, Marten(Jan 2006) Mouse Genetics as a Research Tool. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0005681]