virus express (3-galactosidase, consistent with previ- 
ous findings indicating nonactivity of the viral pro- 
moter in ES cells; however, differentiation of the 
stem cells into embryoid bodies results in activation 
at a high frequency, suggesting expression from the 
viral promoter. Regional, specific staining of the 
embryoid bodies is observed, suggesting influence 
on expression according to the site of integration. 
This result is surprising, since it had been thought 
that the block to viral expression is maintained dur- 
ing further development. Gene trap viral vectors, in 
which the viral promoter has been deleted, have 
been constructed and are being tested. 
III. Targeted Mutagenesis in Transgenic Mice. 
ES cells also allow the possibility of selection for 
mutagenesis of specific genes. Efforts in the labora- 
tory have focused on the gene encoding c-src, 
PUBLICATIONS 
which has been made available by Dr. David Balti- 
more (Whitehead Institute). Constructs designed 
for knockout of c-src activity have been introduced 
into ES cells by electroporation, and homologous 
recombinant clones have been isolated by screen- 
ing with the polymerase chain reaction (PGR) tech- 
nique. With one such construct, including ~8 kb of 
homology, the frequency of such targeted events is 
1 in 100; blot analysis of these clones has demon- 
strated gene targeting, but also rearrangements of 
the mutated allele. The laboratory has also mutated 
the alternate, neuronal splice of c-src in ES cells 
and used both sets of cells for production of chime- 
ras. These animals are being tested for contribution 
to the germline. 
Dr. Soriano is also Assistant Professor of Molecu- 
lar Genetics and of Cell Biology at Baylor College of 
Medicine. 
Books and Chapters of Books 
Soriano, R, Gridley, T, and Jaenisch, R. 1988. Retroviral tagging in mouse development and genetics. In 
Mobile DNA (Howe, M.M., and Berg, D.E., Eds.). Washington, DC: American Society for Microbiology, pp 
927-937. 
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