Mouse models

Question 1

Why mice?

Answer 1

• 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

Question 2

Where are the standard lab mice derived from?

Answer 2

Wild strains of the common field or house mice. Victorian gentlemen breed mice (selecting for spontaneous mutations)

Question 3

What can we do with mice?

Answer 3

• direct matings
• inbred lines/crosses
• KOs
• Transgenics
• mutagenesis
• nuclear transfer
• control exposure to pathogens

Question 4

What are anchors?

Answer 4

Hundreds of bases with >90% identity (represent areas of evolutionary selection)

Question 5

How many base changes roughly have their been in the evolutionary time from mouse to human?

Answer 5

~50%

Question 6

What are inbred strains?

Answer 6

For control experiments, want all mice to to genetically identical. Hence inbred mice stains have been created (via brother-sister matings)

Question 7

What is the congenic dissection approach?

Answer 7

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

Question 8

What are polygenic strains?

Answer 8

Multiple susceptibility intervals reassembled onto a resistant genome, analyses how the different loci interact to produce full spectrum of disease.

Question 9

What is recombinant congenic strains (RC)?

Answer 9

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

Question 10

How do you create a congenic strain?

Answer 10

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

Question 11

What is ENU mutagenesis?

Answer 11

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