As stated in the Banbury
report , a comprehensive catalog of ES cells with a null mutation
for every gene in the mouse genome would provide the floor upon
which additional analyses and experimentation could be done. One
of the advantages of KOMP is that the remaining genes would be
knocked out in a relatively uniform way, thus facilitating downstream
phenotyping in a universal fashion. The uniform molecular biology
that would underlie the KOMP mutagenesis strategy would support
comparative phenotyping studies, which are at present difficult
to perform because each mutant has it's own set of unique molecular
variables. The downstream phenotyping events would be comprised
of separate tiers:
Tier 1: After generating the ES cells or embryos,
mice would be made and run through a broad spectrum of phenotype
analyses, such as tissue expression profiling for the mutated gene.
Tier 2: A subset of these
animals would then be chosen for further in-depth studies which would
include transcriptome analysis and system-specific phenotyping. This
would be funded by individual NIH Institutes and Centers according
to their own interests and scientific priorities.
Tier 3: Specialized phenotpying would be done in
a smaller number of lines which have previously displayed particularly
interesting phenotypes. This would also be funded by individual NIH
institutes in accordance with their own scientific priorities.