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| Decreased apoptosis in the brain and premature lethality in CPP32-deficient mice |
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| Author(s): Kuida K, Zheng TS, Na SQ, Kuan CY, Yang D, Karasuyama H, Rakic P, Flavell RA |
| Source: NATURE Volume: 384 Issue: 6607 Pages: 368-372 Published: NOV 28 1996 |
| Times Cited: 1,272 References: 30 |
| Abstract: PROGRAMMED cell death (apoptosis) is a prominent feature of the development of the immune and nervous systems(1,2). The identification of the Caenorhabditis elegans cell death gene, ced-3, as a prototype of the interleukin-1 beta converting enzyme (ICE) protease family has led to extensive evidence implicating these enzymes in apoptosis(3,4). Among the ten or more members of the ICE protease family, CPP32/yama/apopain(5-7) exhibits the highest similarity to CED-3 in both sequence homolog and substrate specificity(8). To analyse its function in vivo, we generated CPP32-deficient mice by homologous recombination, These mice, horn at a frequency lower than expected by mendelian genetics, mere smaller than their Littermates and died at 1-3 weeks of age, Although their thymocytes retained normal susceptibility to various apoptotic stimuli, brain development in CPP32-deficient mice was profoundly affected, and discernible by embryonic day 12, resulting in a variety of hyperplasias and disorganized cell deployment, These supernumerary cells were postmitotic and terminally differentiated by the postnatal stage, Pyknotic clusters at sites of major morphogenetic change during normal brain development(9) were not observed in the mutant embryos, indicating decreased apoptosis in the absence of CPP32. Thus CPP32 is shown to play a critical role during morphogenetic cell death(9,10) in the mammalian brain. |
| Document Type: Article |
| Language: English |
Addresses:
1. YALE UNIV, SCH MED, HOWARD HUGHES MED INST, IMMUNOBIOL SECT, NEW HAVEN, CT 06510 USA
2. YALE UNIV, SCH MED, NEUROBIOL SECT, NEW HAVEN, CT 06510 USA
3. TOKYO METROPOLITAN INST MED SCI, DEPT IMMUNOL, BUNKYO KU, TOKYO 113, JAPAN |
| Publisher: MACMILLAN MAGAZINES LTD, 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF |
| Subject Category: Multidisciplinary Sciences |
| IDS Number: VV271 |
| ISSN: 0028-0836 |
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