BB3_AG Flashcards
Mus musculus musculus: 30%, eastern Europe
M. m. domesticus: 60%, western Europe
w/ 10% M.m. castaneus (derived from M.m. molossinus)- Asia
= laboratory stock M. musculus
additional strains from M. m. castaneus (Thailand) and M. m. molossinus (Japan) and M. spretus (western Mediterranean region)
Order: Superfamily: Family: Subfamily: Genus:
Order: Rodentia Superfamily: Muroidea Family: Muridae Subfamily: Murinae Genus: Mus
Most inbred laboratory mice share
- maternal mitochondrial genome derived from M.m. domesticus common
- Y chromosome contributed by M.m. musculus through its contribution to the genome of M.m. molossinus (Nagamine et al., 1992).
- Thus, the most inclusive name that can be assigned to the genetically mosaic laboratory mouse is M. musculus, the over-arching name for the entire commensal clade
- C57BL/6 mice contain minor genetic elements derived from M. spretus and a number of wild aboriginal species that are not members of the M. musculus clade, including M. spretus, M. caroli
• 20 pairs of telocentric chromosomes, Arabic numbers in order of decreasing size
o genes located on chromosomes through fish (fluorescent in situ hybridization)
• histocompatibility complex:
H loci control expression of cell surface molecules that modulate critical immune responses such as recognition of foreign tissue
o H2 chromosome 17 is strain dependent
• influences
o Minor H loci are responsible for delayed graft rejection
- Mouse Genome Informatics through Jax catalogs inbred strains, natural mutants, induced mutants, transgenic lines, and targeted mutant lines
- NIH supported Mutant Mouse Regional Centers = repositories
- Mouse Genome Informatics through Jax catalogs inbred strains, natural mutants, induced mutants, transgenic lines, and targeted mutant lines
- NIH supported Mutant Mouse Regional Centers = repositories
• Incross
cross of 2 animals of same homozygous genotype (inbred strain breeding)
o AA x AA
• Outcross:
cross of 2 animals of unrelated genotypes (outbred, breeding 2 inbred strains, breeding any unrelated mice, breeding genetically different F1 mice)
o AA x BB
• Intercross:
cross of 2 animals that are IDENTICALLY heterozygous at a particular locus, a cross between two siblings that are genetically different- F1 of inbred x inbred. Ex breeding siblings for inbred strain
o Aa x Aa
• Backcross:
cross of 2 animals, one heterozygous at a locus and another homozygous for one of those heterozygous alleles
o Aa x aa
• Inbred mouse lines:
strains
o 2- or more brother x sister generations (F)
o syngenic or isogenic to other mice of same strain and sex
o due to residual heterozygozity, not fully inbred until after 60 F generations
o branches = substrains (or even substrains of inbred substrain!)
• if separated before F40
• separated for 100 generations
• Jax said if separated for 20 generations (makes sense since est an inbred strain after 20 generations)
• or if genetic differences arise
• substrain:
inbred strain that is reproductively isolated from its founder inbred strain and has any fixed genetic difference from that strain
• if two inbred strains crossed, F1 hybrids are genetically identical (isogenic) and maximally heterozygous (chromosomes of each chromosomal pair separately contributed by each parental strain)
• segregating inbred strain:
within an inbred strain, heterozygosity forced through backcrossing or intercorssing
• F2 hybrids genetically diverse with chromosomes containing a mixture of contribution from each parental strain
• F2 hybrids genetically diverse with chromosomes containing a mixture of contribution from each parental strain
• Recombinant inbred:
mate offspring from original inbred strain cross
o Each line created from random matings of F2 generation siblings is its own separate inbred strain
o Useful for mapping phenotypic or quantitative traits that differ between the two strains
• Recombinent congenic strains:
sets of inbred strains that breed two inbred strains but then backcross to one parental strain (now called the background strain) after the F1 generation
• Advanced intercross lines
RI where F2 generation of inbred strain avoids sibling matings so increased chance of recombination between tightly linked genes
• Coisogenic:
mutation arises spontaneously or induced within an inbred strain. Virtually identical to the parental inbred strain except for single mutant allele
o Can backcross in which F1 hybrid created by mating donor mutant strain to desired background strain with subsequent matings to background strain while retaining mutant locus
• Requires 10 backcross generations to achieve congenic
• NEVER coisogenic as locus flanked by other DNA
• Outbred:
genetically heterogenous, minimize inbreeding
o Stocks: closed population (for at least four generations) of genetically variable mice bred to maintain maximal heterozygosity
o Most oubtred mice stocks are Swiss origin and derived from nine mice imported to US in 1926 = homogenous genetically
• Consomic:
inbred mice congenic for entire chromosomes- used to study polygenic traits
• Conplastic
mice congenic for different mitochondrial genomes
Genetically Engineered Mice
• Spontaneous mutants, maintained as coisogenic within inbred strain
• Create mutants through radiation mutagenesis, chemical mutagenesis, or transgenesis
o Radiation: in vivo or in vitro (embryonic stem cell)
o Chemical: in vivo male mice or in vitro (embryonic stem cell) with ethylmethanesuphonate (EMS) or N ethy N nitrosourea (ENU) = point mutations
• Transgenic mouse: any mouse in which foreign DNA has been integrated