Down-regulation of dendritic spine and glutamic acid decarboxylase 67 expressions in the reelin haploinsufficient heterozygous reeler mouse

Heterozygous reeler mice (HRM) haploinsufficient for reelin express approxi mate to 50% of the brain reelin content of wild-type mice, but are phenotyp ically different from both wild-type mice and homozygous reeler mice. They exhibit, (i) a down-regulation of glutamic acid decarboxylase 67 (GAD(67))- positive neurons in some but not every cortical layer of frontoparietal cor tex (FPC), (ii) an increase of neuronal packing density and a decrease of c ortical thickness because of neuropil hypoplasia, (iii) a decrease of dendr itic spine expression density on basal and apical dendritic branches of mot or FPC layer III pyramidal neurons, and (iv) a similar decrease in dendriti c spines expressed on the basal dendrite branches of CA1 pyramidal neurons of the hippocampus. To establish whether the defect of GAD(67) down-regulat ion observed in HRM is responsible for neuropil hypoplasia and decreased de ndritic spine density, we studied heterozygous GAD(67) knockout mice (HG(67 )M). These mice exhibited a down-regulation of GAD(67) mRNA expression in F PC (about 50%), but they expressed normal amounts of reelin and had no neur opil hypoplasia or down-regulation of dendritic spine expression. These fin dings, coupled with electron-microscopic observations that reelin colocaliz es with integrin receptors on dendritic spines, suggest that reelin may be a factor in the dynamic expression of cortical dendritic spines perhaps by promoting integrin receptor clustering. These findings are interesting beca use the brain neurochemical and neuroanatomical phenotypic traits exhibited by the HRM are in several ways similar to those found in postmortem brains of psychotic patients.