Abnormal dendritic spines in fragile X knockout mice: maturation and pruning deficits.
Fragile X syndrome arises from blocked expression of the fragile X mental retardation protein (FMRP). Golgi-impregnated mature cerebral cortex from fragile X patients exhibits long, thin, tortuous postsynaptic spines resembling spines observed during normal early neocortical development. Here we describe dendritic spines in Golgi-impregnated cerebral cortex of transgenic fragile X gene (Fmr1) knockout mice that lack expression of the protein. Dendritic spines on apical dendrites of layer V pyramidal cells in occipital cortex of fragile X knockout mice were longer than those in wild-type mice and were often thin and tortuous, paralleling the human syndrome and suggesting that FMRP expression is required for normal spine morphological development. Moreover, spine density along the apical dendrite was greater in the knockout mice, which may reflect impaired developmental organizational processes of synapse stabilization and elimination or pruning.
Comery
T A
TA
Neuroscience Program, University of Illinois, Urbana-Champaign, IL 61801, USA.
Harris
J B
JB
Willems
P J
PJ
Oostra
B A
BA
Irwin
S A
SA
Weiler
I J
IJ
Greenough
W T
WT
D000818:Animals; D002540:Cerebral Cortex / Q000473:pathology / Q000648:ultrastructure*; D003712:Dendrites / Q000473:pathology*; D005260:Female; D005600:Fragile X Syndrome / Q000235:genetics / Q000473:pathology*; D006056:Golgi Apparatus / Q000473:pathology / Q000648:ultrastructure; D006801:Humans; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D009778:Occipital Lobe / Q000473:pathology / Q000648:ultrastructure; D017966:Pyramidal Cells / Q000473:pathology / Q000648:ultrastructure