Caspase-7 Expanded Function and Intrinsic Expression Level Underlies Strain-Specific Brain Phenotype of Caspase-3-Null Mice.
| Title: | Caspase-7 Expanded Function and Intrinsic Expression Level Underlies Strain-Specific Brain Phenotype of Caspase-3-Null Mice. |
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| Authors: | Houde, Caroline1, Banks, Kathleen G.2, Coulombe, Nathalie3, Rasper, Dita3, Grimm, Erich3, Roy, Sophie1,4, Simpson, Elizabeth M.2, Nicholson, Donald W.1,4 donald_nicholson@merck.com |
| Source: | Journal of Neuroscience. 11/03/2004, Vol. 24 Issue 44, p9977-9984. 8p. 1 Color Photograph, 4 Diagrams, 3 Charts, 4 Graphs. |
| Subject Terms: | *BRAIN diseases, *GENES, *ENZYMES, *APOPTOSIS, *DNA |
| Abstract: | Caspase-3-deficient mice of the 129S1/SvImJ (129) strain show severe brain development defects resulting in brain overgrowth and perinatal lethality, whereas on the C57BL/6J (B6) background, these mice develop normally. We therefore sought to identify the straindependent ameliorating gene. We biochemically isolated caspase-7 from B6-caspase-3-null (Casp3-/-) tissues as being the enzyme with caspase-3-1ike properties and capability of performing a caspase-3 surrogate function, apoptotic DNA fragmentation. Moreover, we show that, in contrast to the human enzymes, mouse caspase-7 is as efficient as caspase-3 at cleaving and thus inactivating ICAD (inhibitor of caspase-activated DNase), the inhibitor ofapoptotic DNA fragmentation. Low-levels of caspase-7 expression and activation correlate with lack of DNA fragmentation in 129-Casp3-/- apoptotic precursor neurons, whereas B6-Casp3-/- cells, which can fragment their DNA, show higher levels of caspase-7 expression and activation. The amount of caspase-7 activation in apoptotic precursor neurons is independent of the presence of caspase-3. Together, our findings demonstrate for the first time a strong correlation between caspase-7 activity, normal brain development, and apoptotic DNA fragmentation in Casp3-/- mice. [ABSTRACT FROM AUTHOR] |
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| Database: | Academic Search Complete |
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