Evidence for both neuronal cell autonomous and nonautonomous effects of methyl-CpG-binding protein 2 in the cerebral cortex of female mice with Mecp2 mutation.
Rett syndrome (RTT) is an X-linked neurodevelopmental disorder caused by mutations in the gene MECP2, encoding methyl-CpG-binding protein 2 (MeCP2). Few studies have explored dendritic morphology phenotypes in mouse models of RTT and none have determined whether these phenotypes in affected females are cell autonomous or nonautonomous. Using confocal microscopy analysis we have examined the structure of dendrites and spines in the motor cortex of wild-type (WT) and Mecp2-mutant mice expressing green fluorescent protein (GFP). In Mecp2 GFP female mice age 6-7 months we found significant decreases in the density of spines, width of dendrites, size of spine heads, while increases were found in the length of spine necks, dendritic irregularities, spineless spots, and long spines. We show for the first time that a lower density of spines and smaller spine head area are phenotypes that distinguish MeCP2+ from MeCP2- dendrites in female Mecp2 GFP mice. In Mecp2 GFP male mice at three weeks of age, we found reduced spine density, thinner apical oblique dendrites and increased dendritic irregularities and long spines. Significantly, the changes affected both MeCP2- and MeCP2+ neurons, pointing to the ability of MeCP2- to impact the structure of MeCP2+ neurons. Our findings are evidence that MeCP2 deficiency results in both cell autonomous and nonautonomous changes.
Belichenko
Nadia P
NP
Department of Neurology and Neurological Sciences Stanford University Medical Center, Stanford, CA 94305-5489, USA. pavel_belichenko@yahoo.com
Belichenko
Pavel V
PV
Mobley
William C
WC
D000704:Analysis of Variance; D000818:Animals; D001835:Body Weight; D049229:Dendritic Spines / Q000502:physiology / Q000648:ultrastructure; D005260:Female; D008297:Male; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D009044:Motor Cortex / Q000166:cytology / Q000503:physiopathology*; D009154:Mutation; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D009929:Organ Size; D010641:Phenotype; D012727:Sex Characteristics; D049951:X Chromosome Inactivation
C497393:Mecp2 protein, mouse; D051783:Methyl-CpG-Binding Protein 2