Chapter 18, Problem 19P

Mouse models for human genetic diseases are potentially powerful tools to help geneticists understand the cause of the aberrant phenotypes and develop new therapeutic measures. However, such mice are not always as useful to investigators as it might seem at first glance. Suppose that you have a mouse knockout model for a human disease caused by homozygosity for a null allele of a gene. Discuss how the following situations might complicate investigations of the human disease based on this mouse model.

a.	Mice have a shorter life span than humans.
b.	Mice homozygous for certain knockout mutations die in utero.
c.	Mouse genomes may have additional copies of the gene whose mutation causes the disease in humans.
d.	Mice from different inbred lines homozygous for the same gene knockout vary in the penetrance and expressivity of the phenotype.
e.	Manipulations to create the knockout mouse, such as the presence of a drug resistance gene that allows the selection of cells containing the knockout (see Fig. 18.9), can disrupt not only the targeted gene, but also the expression of other, nearby genes.