The dramatic increase in sequence information in the form of expressed
sequence tags (ESTs)(1) and genomic sequence has created a 'gene func
tion gap', with the identification of new genes far outpacing the rate
at which their function can be identified. The ability to create muta
tions in embryonic stem (ES) cells on a large scale by tagged random m
utagenesis provides a powerful approach for determining gene function
in a mammalian system; this approach is well established in lower orga
nisms(2,3). Here we describe a high-throughput mutagenesis method base
d on gene trapping that allows the automated identification of sequenc
e tags from the mutated genes, This method traps and mutates genes reg
ardless of their expression status in ES cells, To facilitate the stud
y of gene function on a large scale, we are using these techniques to
create a library of ES cells called Omnibank, from which sequence-tagg
ed mutations in 2,000 genes are described.