For biomedical research involving laboratory animals to be effective in the sense that results from different laboratories can be compared and evaluated, there must be recognized criteria for animal care, including definitions of animal health status and genetic constitution. Genetic uniformity, which facilitates reproducibility of experiments, is highly desirable in experimentation with animals and should be utilized wherever practicable. Comparisons among results derived from work with different genetically defined types within the same species may add to the significance of those findings. In certain mammalian species, especially the mouse, and to a lesser degree the rat, guinea pig, and hamster, the availability of a great variety of genetically defined stocks provides research workers with precise experimental material.

Other species, in which genetically completely homogeneous animals are not available, are also essential for research. For these species, clear recognition of the genetic status of each stock, provision of as much genetic information as feasible, and colony management designed to avoid genetic differentiations within a single colony are all desirable goals.

1. Definitions: Laboratory Animal Genetics

a) Outbred Stock

In laboratory animal science, outbred stocks (the term "stock" is reserved for outbred animals) are closed colonies of animals that are not uniformly homozygous, that is, they are not inbred. Common stocks such as Sprague-Dawley, Long-Evans and Wistar rats are similar to "breeds" of sheep or dogs in that they differ from one another in the genes which are fixed within the stock. The primary objective in the maintenance of an outbred stock is to ensure that the stock remains constant in all characteristics for as many generations as possible. For the stock to stay constant, it must be maintained as closed colony without selection, in such a way as to give less than 1% inbreeding per generation. In the breeding of agricultural animals, breeders use constant selection pressure to improve desirable traits. The laboratory animal breeder wants to avoid any selection pressure. In order to avoid inbreeding or the loss of alleles, colonies of outbred animals must not be maintained in small colonies (less than 30 breeding pairs). Investigators who breed outbred stocks for experimental purposes (e.g. to study embryos, neonates, or maternal behavior), should periodically go back to an established colony to replenish breeding stock.

b) Inbred Strain

In general use, the term "inbreeding" refers to the breeding of related individuals, which results in a trend toward increased homozygosity. In rodent genetics, "inbred" has a very specific meaning.

Each inbred strain (the term "strain" is reserved for inbred animals) is the result of 20 or more consecutive generations of single-pair brother x sister mating, in which all animals trace back to a single breeding pair in the 20th or subsequent generations. After 20 generations, individuals of an inbred strain can be expected to be homozygous at 98.6 percent of their loci.

As a result, all individuals in an inbred strain are "isogenic" or genetically identical. Inbred strains are invaluable in studies involving tissue transfer such as tissue grafts and tumor studies.

There can only be one holder of a given inbred strain in the world at any one time. Animals derived from an inbred strain but maintained separately for 10 generations are considered a substrain.

c) Transgenics

Transgenic animals are animals (and their descendants) which were created by the introduction of foreign DNA into their chromosomes during early embryonic development. These animals contain transferred genes. Transgenics can be produced through pronuclear microinjection, retrovirus-mediated transgenesis, embryonic stem cell cell-mediated transgenesis, nuclear transplantation (cloning), transfer of chromosomal fragemenets, gamete transfection and IVF, and direct injection of DNA into skeletal muscle.

d) F1 Hybrids

An F1 hybrid is a first generation cross between two inbred strains. Individual F1 hybrids of a specific cross are genetically identical to one another, but are heterozygous at all alleles in which the parental strains differed. F1 hybrids do not breed true but can be produced repeatedly by crossing the parental inbred strains. F1 hybrids are more vigorous than inbred strains. They will grow tumors or accept skin grafts from each other and from either parental strain.

e) Mutant Stocks

A mutant stock is any outbred stock that carries a specific Mendelian mutation. The nude gene ("nu") is an example of a mutation in mice. When a mutation occurs in an inbred strain or can be placed within an inbred strain by suitable breeding techniques, the resulting strains are known as "coisogenic", "congenic" or "segregating inbred" strains. These are discussed below.

f) Coisogenic Strains

A pair of inbred strains that differ at only a single genetic locus, resulting from a mutation occurring within an established inbred strain followed by separation into mutant-bearing and normal sublines are said to be "coisogenic".

f) Congenic Strains

When a mutation that occurs is not in an inbred strain, a state that approaches coisogenicity can be produced by backcrossing the mutation to an inbred strain for several (preferably 12) generations. Such a segregating strain is known as a congenic strain.

g) Genetic Drift

When a mutation that occurs is not in an inbred strain, a state that approaches coisogenicity can be produced by backcrossing the mutation to an inbred strain for several (preferably 12) generations. Such a segregating strain is known as a congenic strain.

h) Gnotobiotic

The word gnotobiotic is derived from the Greek words gnotos and biota meaning known flora or fauna. Therefore, when referring to gnotobiotes, one refers to an animal with a known microbial flora.

2. Concerns With Raising a Colony

limit genetic drift

follow proscribed mating procedures (generally bxs)

should be monitored

avoid genetic contamination (mutation, mismating)

maintain heterogeneity of gene pool (avoid bottleneck)

Virus free

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