• homozygous mice are indistinguishable from wild-type mice

• exposure to environmental enrichment following contextual fear conditioning results in a significant increase in freezing responses during retention tests

• environmental enrichment induces significantly less neurogenesis in the dentate gyrus of the brain in mutants compared to wild-type controls

• following environmental enrichment the number of newborn neurons in the subgranular zone and molecular layer of the dentate gyrus are 39% and 48% less respectively compared to wild-type mice

• by 10 months of age mutants have impaired performance in a novel object recognition test

• by 10 months of age some mutants show increased activity in an open field test

• a dramatic increase in apoptosis is seen in the degenerating forebrain

• by 10 months of age mutant mice start to show reduced body weights compared to wild-type

• the lateral ventricles are immensely enlarged compared to wild-type or single knockout mice

• the third ventricle is immensely enlarged compared to wild-type or single knockout mice

• the thickness of the corpus callosum is about a third that of controls

• the thickness of the molecular layers between the CA1 pyramidal cells and dentate gyrus is significantly reduced

• the cortex is about half the normal thickness and the 6 layers can no longer be distinguished

• increased Gfap expression indicates that reactive astrogliosis occurs along with forebrain degeneration

• changes in the expression of several markers indicate that neuronal atrophy occurs along with forebrain degeneration

• degeneration is seen in the forebrain