Abnormal dendritic spines in fragile X knockout mice: Maturation and pruning deficits

Abnormal dendritic spines in fragile X knockout mice: Maturation and pruning deficits

^*Neuroscience Program, Departments of ^†Biology, ^‖Psychology, ^**Psychiatry, and ^‡‡Cell and Structural Biology, and ^‡Beckman Institute, University of Illinois, Urbana-Champaign, IL 61801; ^§Department of Medical Genetics, University of Antwerp, 2610 Antwerp, Belgium; and ^¶Department of Clinical Genetics, Erasmus University, 3015 GE, Rotterdam, The Netherlands

Abstract

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.

Footnotes

↵ †† To whom reprint requests should be addressed at: Beckman Institute, 405 North Mathews Avenue, Urbana, IL 61801. e-mail: greenough{at}uiuc.edu.
William T. Greenough
ABBREVIATIONS:

FMRP,

fragile X mental retardation protein;

FMR1,

fragile X mental retardation gene or mRNA;

Fmr1,

mouse FMR1 gene