Targeted Gene Disruption in Transgenic Mice

The specific experimental inactivation of a gene
affords an opportunity to study its normal function
by comparing it with that of the inactive
state. This will yield information about the role
of a particular gene in development or other
functions that would not be available otherwise.
In the approach described here, a normal
gene is replaced by a mutant allele by disrupting
the normal gene (targeted gene disruption).
The effects can be studied in different embryonic
stages of mouse development and after
birth. Subsequently the results can be compared
to the effects ofmutations in homologous
human genes as seen in human genetic diseases.
The method requires the use of mouse
embryonic stem (ES) cells. ES cells are
pluripotential, i.e., they are capable of giving
rise to different kinds of cells but not to an entire
organism. These cells can be grown in culture
through many generations and yet retain
the potential to be integrated into a mouse blastocyst.
Here they participate in embryonic
development allowing mice to produce that are
homozygous for a mutation introduced into a
specific gene (knockout mice).