DNA fragmentation factor 45 deficient mice exhibit enhanced spatial learning and memory compared to wild-type control mice

Programmed cell death or apoptosis is a highly regulated physiological proc ess that is critical in development, particularly in the central nervous sy stem. The DNA fragmentation factor 45 (DFF45 or ICAD) is a subunit of a het erodimeric DNase complex that is crucial for DNA fragmentation and normal a poptosis. To examine the neurobiological consequences of lacking DNA fragme ntation and timely apoptosis during mouse development in vivo, we compared spatial learning behaviors in DFF45 mutant and wild-type control mice. We f ound that DFF45 mutant mice exhibit enhanced spatial learning and memory co mpared to wild-type mice. Moreover, both the granule cell density and total granule cell number in the hippocampal dentate gyrus region are higher in thr DFF45 mutant brains than in the wild-type brains. We propose that the i ncrease in granule cell number in the dentate region due to the DFF45 mutat ion changes the neuronal network underlying spatial learning and memory in DFF45 mutant mice. (C) 2000 Elsevier Science B.V. All rights reserved.