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Caspases play a key role during
apoptotic execution. In an attempt to elucidate the specific role of caspase-7
we generated a chicken DT40 cell line in which both alleles of the gene were
disrupted. Viability assays showed that caspase-7 -/- clones are more resistant
to the common apoptosis-inducing drugs etoposide and staurosporine. Caspase-7 -/- cells show
a delay in phosphatidylserine externalization and DNA
fragmentation as well as cleavage of the caspase
substrates PARP and lamins B1 and B2. Caspase affinity labeling and activity assays indicated
that deficient cells exhibit a delay in caspase
activation when compared to wild type DT40 cells, providing an explanation for
the differences in apoptotic execution between caspase-7 null and wild type
DT40 cells. These results strongly suggest that caspase-7 is involved earlier
than other effector caspases
in the apoptotic execution process in DT40 B lymphocytes.l