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Hybrids and Outbred Mice


F1 Hybrids
The most obvious advantage of working with inbred strains is genetic uniformity over time and space. Researchers can be confident that the B6 mice used in experiments today are essentially the genetic equivalent of B6 mice used ten years ago. Furthermore, one can be confident that there will always be B6 mice around to conduct experiments on. Thus, the existence of inbred strains serves to eliminate the contribution of genetic variability to the interpretation of experimental results. However, there is a serious disadvantage to working with inbred mice in that a completely inbred genome is an abnormal condition with detrimental phenotypic consequences. The lack of genomic heterozygosity is responsible for a generalized decrease in a number of fitness characteristics including body weight, life span, fecundity, litter size, and resistance to disease and experimental manipulations.

It is possible to generate mice that are genetically uniform without suffering the consequences of whole genome homozygosity. This is accomplished by simply crossing two inbred strains. The resulting F1 hybrid animals express hybrid vigour in all of the fitness characteristics just listed with an overall life span that will exceed that of both inbred parents (Green and Witham, 1991). Furthermore, as long as there are both B6 mice and DBA mice, for example, it will be possible to produce F1 hybrids between the two, and all F1 hybrids obtained from a cross between a B6 female and a DBA male will be genetically identical to each other over time and space. This particular F1 hybrid is the most common of those used. All F1 hybrid animals are named with an abbreviated form of the female progenitor first, followed by the male progenitor and the "F1" symbol. The F1 hybrid generated from a cross between B6 females and DBA/2 males is named B6D2F1. Of course, uniformity will not be preserved in the offspring that result from an "intercross" between two F1 hybrids; instead random segregation and independent assortment will lead to F2 animals that are all genotypically distinct.

Outbred Stocks
A large number of the laboratory mice sold and used by investigators around the world are considered to be outbred or random-bred. Outbred mice are used for the same reasons as F1 hybrids — they exhibit hybrid vigour with long life spans, high disease resistance, early fertility, large and frequent litters, low neonatal mortality, rapid growth and large size. However, unlike F1 hybrids, outbred mice are genetically undefined. Nevertheless, outbred mice are bought and used in large numbers simply because they are less expensive than any of the genetically-defined strains.

Outbred mice are useful in experiments where the precise genotype of animals is not important and when they will not contribute their genome toward the establishment of new strains. They are often ideal as a source of material for biochemical purification and as stud males for the stimulation of pseudo-pregnancy in females to be used as foster mothers for transgenic or chimeric embryos. It is unwise to use outbred males as progenitors for any strain of mice that will be maintained and studied over multiple generations; the random-bred parent will contribute genetic uncertainty which could result in unexpected results down the road.

If a stock of mice were truly random bred, it would be maintained through matings that were set up randomly among the breeding-age members of the population. Accordingly, matings would sometimes occur between individuals as closely related as siblings. In fact, most commercial suppliers follow breeding schemes that avoid crosses between closely related individuals in order to maintain the maximal level of heterozygosity in all offspring. Thus, random-bred is a misnomer; stocks of this type should always be called non-inbred or outbred.

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