Mouse models Flashcards
Why mice?
- similar to human biologically & genetically (genome size and number of genes)
- degree of sequence homology to humans
- high reproduction rate (~100 pups per year)
- short lifespan (mature quickly)
- inexpensive; easy to handle and care for
Where are the standard lab mice derived from?
Wild strains of the common field or house mice. Victorian gentlemen breed mice (selecting for spontaneous mutations)
What can we do with mice?
- direct matings
- inbred lines/crosses
- KOs
- Transgenics
- mutagenesis
- nuclear transfer
- control exposure to pathogens
What are anchors?
Hundreds of bases with >90% identity (represent areas of evolutionary selection)
How many base changes roughly have their been in the evolutionary time from mouse to human?
~50%
What are inbred strains?
For control experiments, want all mice to to genetically identical. Hence inbred mice stains have been created (via brother-sister matings)
What is the congenic dissection approach?
Involves taking the region mapped by linkage using disease prone mouse and backcross onto a mouse that doesn’t have the disease. Congenic strains then analysed as Mendelian traits. Can map the different phenotypic components of the disease to different loci
What are polygenic strains?
Multiple susceptibility intervals reassembled onto a resistant genome, analyses how the different loci interact to produce full spectrum of disease.
What is recombinant congenic strains (RC)?
Breeding technique that utilizes two strains of a species, via backcrossing and inbreeding, to isolate the genetic locus associated with a particular disease. Helps tease apart complex genetic interactions linked to a disease of trait
How do you create a congenic strain?
Donor (only involved in initial cross) whose phenotype is associated with a genetic disease is crossed with a recipient (healthy strain). Number of backcrosses and inbreeding matings will vary depending on the specific genomic proportions desired
What is ENU mutagenesis?
N-ethyl-N-nitrosourea (ENU)
- very high mutation rate
- generates point mutations
- screen 300-500 mouse lines to test for new mutations in every gene
- mapping the mutation is difficult
- results in F1 ENU mutants with visible phenotypes