Strain Development Flashcards
What was the first inbred strain?
DBA
How is an inbred strain made? How many generations to be inbred vs. fully inbred vs. most strains today?
Brother x sister matings. Inbred = 20 generations, fully inbred = 60 generations, most = >200 generations.
What terms (2) refer to genetically identical strains?
Syngenic or isogenic
What causes a strain to be designated a substrain?(3)
- Separated after F20 but before F40
- Inbred branches separated for 100 generations
- Genetic differences
What does a cross of two inbred strains create? Describe their genetic identity and level of homozygosity.
F1 generation, genetically identical and maximally heterozygous
What does a cross of F1 siblings result in? Describe their genetic diversity.
F2, maximally genetically diverse
How are RI strains developed?
Two inbred strains are crossed to create F1, with at least 20 generations of F1 brother-sister matings to create F2.
When are RI strains inbred?
After 20 additional brother-sister matings of F2. Creates a ‘set of RI strains.’
How does each line in a set of RI strains differ from each other?
Phenotypic or quantitative traits that differed between progenitor strains. Strains contain unique, approx. equal proportions of genetic contributions from two original progenitor strains.
What is the Collaborative Cross (CC) set of strains?
Derived from 8 inbred strains, captures 90% of known genetic variability. Five classical inbred strains (129S1/SvImJ, A/J, C57BL/6J, NOD/ShiLtJ, and NZO/HlLtJ) and three wildtype-derived strains (CAST/EiJ, PWK/PhJ, WSB/EiJ)
What is a recombinant congenic strain and how is it developed?
Similar to a RI strain but with backcrossing to one parental strain (background strain) after F1 but before inbreeding. Other parental strain is the donor strain.
What determines the proportion of the genome in a recombinant congenic strain?
Number of backcrosses
How is a advanced intercross line (AIL) developed? Why is this type of mating selected?
As for a RI line, but with nonsibling matings from the F2 generation. increases the possibility of recombination between tightly linked genes.
What is a co-isogenic line?
Identical except for a single mutant allele.
How and why are congenic lines developed?
If a co-isogenic mutation is desired in a different strain, co-isogenic mice are backcrossed to create a F1 hybrid with the desired allele on the desired background. After 10 generations the mice are congenic.
How are co-isogenic and congenic mice different?
Congenic mice have desired allele surrounded by flanking DNA from original strain.
How are outbred stocks developed?
Heterogenous with minimized inbreeding. Closed population for at least 4 generations.
Outbred stocks are primarily from what origin? What does this predispose these animals to?
Swiss origin from 9 mice, leading to a high degree of homozygosity. Predisposed to blindness due to rd1 allele.
Describe consomic
Strains with chromosome substitution, congenic for entire chromosomes
Describe conplastic
Congenic for different mitochondrial genomes
Define random bred stock
Random matings within a large, heterogenous population. Continued via random mating with selection of pairs with random numbers.
How are F1 hybrids created and maintained?
Developed from crosses between inbred strains. Cannot be perpetuated.
How are inbred strains perpetuated?
Continue brother-sister matings.
Describe segregating inbred strains. (4)
Brother-sister matings for more than 20 generations. Heterozygosity for mutations forced by:
1. Backcrossing
2. Intercrossing
3. Crossing and intercrossing
4. Backcrossing and intercrossing
How to perpetuate mutation in coisogenic inbred strains? (4)
- Brother-sister matings within strain of origin
- Backcross or cross-intercross system with strain of origin as parent strain
- Brother-sister mating with heterozygosity forced by back- or intercrosses
- Brother-sister mating between homozygotes
How to develop a congenic inbred strain (2)
- Repeated backcross of mutation-bearing mice for 10 or more generations
- Cross-intercross system for the equivalent of 20 or more cycles with an inbred parent strain
What is an incross?
Mating of like homozygotes. Offspring are homozygotes and identical to parents. Used to maintain strain.
What is a outcross?
Mating of unlike homozygotes. Offspring are hybrids, F1. All offspring genetically identical.
What is a backcross?
Mating of a heterozygote and homozygote. F1 mouse and inbred mouse for a given locus.
What is an intercross?
Mating of hybrid brother sisters (F1 generation). Resulting F2 not genetically identical, follows Mendelian genetics. Segregates for loci in which original parental strains differ.
What is the purpose of backcrossing? What does this create?
Transfer a donor gene onto a recipient background by backcrossing. Creation on congenic mouse with a change to a single gene/locus on an inbred strain.
Describe coisogenic strains. How are they developed?
Inbred strains that differ at only a single locus. Occur through spontaneous mutation, target mutation, or chemical or radiation-induced mutation.
