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Mouse Crosses and Standard Strains


Outcrosses, Backcrosses, Intercrosses, and Incrosses
A formal classification system has been developed to describe the various types of crosses that can be set up between mice having defined genetic relationships relative to each other at one or more loci. For the sake of simplicity in describing these crosses, I will arbitrarily use a single locus (the A locus) with two alleles (A and a) to represent the situation encountered for the whole genome. With a simple two allele system, there are only four generalised classes of crosses that can be carried out: each of these is described in more detail in the following discussion.

At the start of most breeding experiments, there is usually an outcross, which is defined as a mating between two animals or strains considered unrelated to each other. In many experiments, the starting material for this outcross is two inbred strains. As described in the next section, all members of an inbred strain are, for all practical purposes, homozygous across their entire genome and genetically identical to each other. Thus, an outcross between two inbred strains can be symbolized as A/A x a/a, and the offspring resulting from such a cross are called the first filial generation, symbolized by F1. All F1 animals that derive from an outcross between the same pair of inbred strains are identical to each other with a heterozygous genome symbolized as A/a. However, when either or both parents are not inbred, F1 siblings will not be identical to each other.

An outcross between two inbred strains or between one inbred strain and a non- inbred animal that contains a genetic variant of interest is almost always the first breeding step performed in a linkage analysis. The F1 animals obtained from this outcross can be used in two types of crosses commonly performed by mouse geneticists – backcrosses and intercrosses. A mating between a heterozygous F1 animal (with an A/a genotype) and one that is homozygous for either the A or a allele is called a backcross. This term is derived from the vision of an F1 animal being mated "back" to one of its parents. In actuality, a backcross is usually accomplished by mating F1 animals with other members of a parental strain rather than a parent itself. The two generation outcross-backcross combination is one of the major breeding protocols used in linkage analysis. From Mendel's first law of segregation, we know that the offspring from a backcross to the a/a parent will be distributed in roughly equal proportions between two genotypes at any single locus - approximately 50% will be heterozygous A/a, and approximately 50% will be homozygous a/a.

A mating set up between brothers and sisters from the F1 generation, or between any other two animals that are identically heterozygous at a particular locus under investigation, is called an intercross. The two generation outcross-intercross series was the classic breeding scheme used by Mendel in the formulation of his laws of heredity, and it is the second major breeding protocol used today for linkage analysis in mice. Again, according to Mendel's first law, the offspring from an intercross will be distributed among three genotypes at any single locus - 50% will be heterozygous A/a, 25% will be homozygous A/A, and 25% will be homozygous a/a.

A mating between two members of the same inbred strain, or between any two animals having the same homozygous genotype is called an incross. The incross serves primarily as a means for maintaining strains of animals that are inbred or carry particular alleles of interest to the investigator. All offspring from an incross will have the same homozygous genotype which is identical to that present in both parents.

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