Delayed maturation of neuronal architecture and synaptogenesis in cerebral cortex of Mecp2-deficient mice.
We detected morphologic abnormalities in the cerebral cortex of Mecp2-hemizygous (Mecp2(-/y)) mice. The cortical thickness of both somatosensory and motor cortices in mutants did not increase after 4 weeks of age, as compared with that in wild-type male mice. The density of neurons in those areas was significantly higher in layers II/III and V of Mecp2(-/y) mice than in wild-type mice, particularly in layers II/ III after 4 weeks of age. In layer II/III of the somatosensory cortex of Mecp2(-/y) mice, the diameter of the apical dendrite was thin and the number of dendritic spines was small. Electron microscopy revealed that two-week-old mutants already had numerous premature postsynaptic densities. These results indicate that Mecp2(-/y) mice suffered delayed neuronal maturation of the cerebral cortex and that the initial neuronal changes were caused by premature synaptogenesis. Rett syndrome patients with a heterozygous mutation of Mecp2 display developmental disorders including cortical malfunctions such as mental retardation, autism, and epilepsy. Our results provide evidence of the similarity with Rett syndrome brains in some respects and suggest that MeCP2/Mecp2 plays some role in synaptogenesis.
Department of Mental Retardation and Birth Defect Research, Institute of Neuroscience, National Center for Neurology and Psychiatry, Kodaira, Tokyo, Japan.
Tetsuya
T
Fukuda
Masayuki
M
Itoh
Tomio
T
Ichikawa
Kazuo
K
Washiyama
Yu-ichi
Y
Goto
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D002452:Cell Count; D048429:Cell Size; D002540:Cerebral Cortex / Q000254:growth & development / Q000473:pathology / Q000503:physiopathology; D002868:Chromosomal Proteins, Non-Histone / Q000172:deficiency*; D004268:DNA-Binding Proteins / Q000172:deficiency*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D051783:Methyl-CpG-Binding Protein 2; D051379:Mice; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission / Q000379:methods; D009474:Neurons / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D010320:Parvalbumins / Q000378:metabolism; D012097:Repressor Proteins; D016622:Silver Staining / Q000379:methods; D013569:Synapses / Q000473:pathology* / Q000648:ultrastructure
D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D005904:Glial Fibrillary Acidic Protein; C497393:Mecp2 protein, mouse; D051783:Methyl-CpG-Binding Protein 2; D010320:Parvalbumins; D012097:Repressor Proteins