Abstract
Using an in vitro apoptosis system, we have previously identified a novel nuclear factor designated Acinus that is a substrate of caspase-3 and responsible for apoptotic chromatin condensation. In this research, we performed the conditional gene targeting using the Cre/loxP system in order to study the role of Acinus in apoptosis and the function of Acinus in mammalian development and adult tissues.Mutant mice were generated in which 8 exons encoding the region important for the chromatin condensation activity of Acinus were flanked by loxP sites. These mutant mice were mated with CAG-Cre transgenic mice to obtain Acinus +/- mice. No homozygous Acinus -/- mice were obtained from interbreeding heterozygous Acinus +/- mice. Analysis of embryos at different stages of gestation indicated that Acinus -/- mutant embryos were smaller than Acinus +/+ and Acinus +/- embryos and did not survive past E12.5. Additionally, targeted deletion of Acinus that was restricted to the T-cell lineage caused a defect in T-cell maturation. These results suggested that Acinus plays an important role in mammalian development and T-cell maturation. [Jpn J Physiol 54 Suppl:S226 (2004)]
