Breeding Programmes

Random or Outbred Stocks

Although random and outbred are often used interchangeably the systems of mating differs. Random infers that the mating system is by chance. Outbreeding is not a chance selection, but a scheduled production in which brother-sister mating is avoided. Several systems of outbreeding are recognised but the common aim of both systems is that the population as a whole is represented by as large a range of alleles of each gene as possible resulting in an inbreeding coefficient of no greater than 2% per generation.

Inbred Strains

A strain is regarded as inbred when it has been brother-sister mated for 20 or more consecutive generations (F20). Parent-offspring mating may be substituted for brother-sister matings provided that the mating in each case is to the younger of the two parents. After 20 generations the coefficient of inbreeding is in excess of 98.6%. Inbred animals are isogenic (individuals are genetically identical) and therefore members of a strain are histocompatible. However, the individuals of a given strain regardless of the number of inbred generations beyond 20 never reach a state of complete homozygosity although animals should be homozygous at more than 99% of their genetic loci. Most inbred strains at the ARC are maintained as a nucleus of 10 pairs per generation. The progeny of the nucleus that is not selected for the next generation is either held as stock for sale or is used for the production (expansion) colonies. Production of large numbers of animals is performed according to the “traffic-light” system as follows: Pedigree stock from the nucleus is random-mated in boxes with white labels. Progeny from these matings is used to establish the first generation breeding stock (green labels). First generation offspring are sold or used for the second generation breeding stock (yellow labels). The offspring of the second generation are sold or used for the third generation (red labels). All progeny of the third generation are sold.

Congenic Strains

A congenic strain is an inbred strain that is genetically identical to an established inbred except for a short chromosomal segment bearing the gene of interest. The formation of a congenic strain begins with the crossing of two breeding groups. One provides the genetic background and must always be an inbred strain. The other is the donor that carries the gene of interest and may or may not be an inbred strain. The mating system used to produce congenic strains depends upon whether the gene in question is dominant or recessive and the effect of the gene, when homozygous, on reproductive performance. Generally, ten backcross generations are required before the strain is considered to be congenic. Once established, a congenic strain is managed identically to an inbred strain.

Hybrids

A hybrid is the first generation progeny (F1) of parents from two different inbred strains. Genetic uniformity and hybrid vigour are two of the desirable features of hybrids. They are typically not bred except to demand, as the unique features cannot be maintained into the F1+ generations. Hybrids are named with the female strain first and the name is commonly shortened. For example the C57BL/6J (Female) x DBA/2 (Male) = B6D2F1, and C57BL (Female) x BALB/c (Male) = BCF1.

Mutant Strains

As the name implies this type of animal displays a feature of a genetic mutation. It may be as simple and benign as a coat-colour mutation or a complex mutation in which the animal is sexually infertile or is predisposed to a disease state or death. The mutation of interest can be transferred in most cases to both outbred and inbred animals. For example, the Animal Resources Centre carries the athymic nude mutation of mice on both an outbred background (Swiss albino) as well as on an inbred background (BALB/c). Mutations can be either spontaneous (eg. Foxn1nu/Foxn1nu, hr/hr) or induced (transgenic and knockout strains).

Recombinant Inbred Strains.

Recombinant inbred (RI) strains are those which have been derived from the cross of two unrelated but highly inbred progenitor strains and which have been maintained independently under a regimen of strict inbreeding since the F2 generation as separate parallel lines. A minimum of twenty generations of inbreeding is required thereafter. This results in numerous separate inbred strains derived from a two inbred strains. These lines can be used to investigate whether a trait is polygenic or controlled by a single gene.