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 approximately 50% of the brain reelin content of wild-type mice, but are phenotypically 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 cortex (FPC), (ii) an increase of neuronal packing density and a decrease of cortical thickness because of neuropil hypoplasia, (iii) a decrease of dendritic spine expression density on basal and apical dendritic branches of motor FPC layer III pyramidal neurons, and (iv) a similar decrease in dendritic spines expressed on the basal dendrite branches of CA1 pyramidal neurons of the hippocampus. To establish whether the defect of GAD(67) down-regulation observed in HRM is responsible for neuropil hypoplasia and decreased dendritic spine density, we studied heterozygous GAD(67) knockout mice (HG(67)M). These mice exhibited a down-regulation of GAD(67) mRNA expression in FPC (about 50%), but they expressed normal amounts of reelin and had no neuropil hypoplasia or down-regulation of dendritic spine expression. These findings, coupled with electron-microscopic observations that reelin colocalizes 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 because 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.
Psychiatric Institute, Department of Psychiatry, College of Medicine, University of Illinois, Chicago, IL 60612, USA.
W S
WS
Liu
C
C
Pesold
M A
MA
Rodriguez
G
G
Carboni
J
J
Auta
P
P
Lacor
J
J
Larson
B G
BG
Condie
A
A
Guidotti
E
E
Costa
D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000378:metabolism*; D003712:Dendrites / Q000378:metabolism*; D015536:Down-Regulation; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D005625:Frontal Lobe / Q000378:metabolism; D015870:Gene Expression; D005968:Glutamate Decarboxylase / Q000235:genetics / Q000378:metabolism*; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008818:Mice, Neurologic Mutants; D009419:Nerve Tissue Proteins; D010296:Parietal Lobe / Q000378:metabolism; D012333:RNA, Messenger; D000091042:Reelin Protein; D012697:Serine Endopeptidases; D013131:Spine / Q000378:metabolism*
D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D007527:Isoenzymes; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D000091042:Reelin Protein; C000717128:Reln protein, mouse; D012697:Serine Endopeptidases; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1; C401141:glutamate decarboxylase 2