Mouse models for human genetic diseases are potentially powerful tools to help geneticists understand thecause of the aberrant phenotypes and develop newtherapeutic measures. However, such mice are not always as useful to investigators as it might seem at firstglance. Suppose that you have a mouse knockoutmodel for a human disease caused by homozygosityfor a null allele of a gene. Discuss how the followingsituations 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 mutationsdie in utero.c. Mouse genomes may have additional copies of thegene whose mutation causes the disease in humans.d. Mice from different inbred lines homozygous forthe same gene knockout vary in the penetrance andexpressivity of the phenotype.e. Manipulations to create the knockout mouse, suchas the presence of a drug resistance gene that allowsthe selection of cells containing the knockout (seeFig. 18.9), can disrupt not only the targeted gene,but also the expression of other, nearby genes.
Mouse models for human genetic diseases are potentially powerful tools to help geneticists understand the
cause of the aberrant
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.
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