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Methyl CpG-Binding Protein 2 (a Mutation of Which Causes Rett Syndrome) Directly Regulates Insulin-Like Growth Factor Binding Protein 3 in Mouse and Human Brains

Itoh, Masayuki ; Ide, Shuhei ; Takashima, Sachio ; Kudo, Shinichi ; Nomura, Yoshiko ; Segawa, Masaya ; Kubota, Takeo ; Mori, Hideo ; Tanaka, Shigeki ; Horie, Hiroshi ; Tanabe, Yuzo ; Goto, Yu-ichi

Journal of neuropathology and experimental neurology, 2007-02, Vol.66 (2), p.117-123 [Periódico revisado por pares]

Hagerstown, MD: American Association of Neuropathologists, Inc

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Título:
Methyl CpG-Binding Protein 2 (a Mutation of Which Causes Rett Syndrome) Directly Regulates Insulin-Like Growth Factor Binding Protein 3 in Mouse and Human Brains
Autor: Itoh, Masayuki ; Ide, Shuhei ; Takashima, Sachio ; Kudo, Shinichi ; Nomura, Yoshiko ; Segawa, Masaya ; Kubota, Takeo ; Mori, Hideo ; Tanaka, Shigeki ; Horie, Hiroshi ; Tanabe, Yuzo ; Goto, Yu-ichi
Assuntos: Adolescent ; Adult ; Animals ; Binding Sites - genetics ; Biological and medical sciences ; Brain - growth & development ; Brain - metabolism ; Brain - physiopathology ; Cell Count ; Cerebral Cortex - growth & development ; Cerebral Cortex - metabolism ; Cerebral Cortex - physiopathology ; Child ; Female ; Gene Expression Regulation, Developmental - genetics ; Humans ; Insulin-Like Growth Factor Binding Protein 3 ; Insulin-Like Growth Factor Binding Proteins - genetics ; Insulin-Like Growth Factor Binding Proteins - metabolism ; Male ; Malformations of the nervous system ; Medical sciences ; Methyl-CpG-Binding Protein 2 - genetics ; Methyl-CpG-Binding Protein 2 - metabolism ; Mice ; Mice, Knockout ; Mice, Transgenic ; Neurology ; Promoter Regions, Genetic - genetics ; Protein Binding - genetics ; Regulatory Elements, Transcriptional - genetics ; Rett Syndrome - genetics ; Rett Syndrome - metabolism ; Vascular diseases and vascular malformations of the nervous system
É parte de: Journal of neuropathology and experimental neurology, 2007-02, Vol.66 (2), p.117-123
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
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Descrição: Rett syndrome (RTT) is a major neurodevelopmental disorder, characterized by mental retardation and autistic behavior. Mutation of the MeCP2 gene, encoding methyl CpG-binding protein 2, causes the disease. The pathomechanism by which MeCP2 dysfunction leads to the RTT phenotype has not been elucidated. We found that MeCP2 directly regulates expression of insulin-like growth factor binding protein 3 (IGFBP3) gene in human and mouse brains. A chromatin immunoprecipitation assay showed that the IGFBP3 promoter contained an MeCP2 binding site. IGFBP3 overexpression was observed in the brains of mecp2-null mice and human RTT patients using real-time quantitative polymerase chain reaction and Western blot analyses. Moreover, mecp2-null mice showed a widely distributed and increased number of IGFBP3-positive cells in the cerebral cortex, whereas wild-type mice at the same age showed fewer IGFBP3-positive cells. These results suggest that IGFBP3 is a downstream gene regulated by MeCP2 and that the previously reported BDNF and DLX5 genes and MeCP2 may contribute directly to the transcriptional expression of IGFBP3 in the brain. Interestingly, the pathologic features of mecp2-null mice have some similarities to those of IGFBP3-transgenic mice, which show a reduction of early postnatal growth. IGFBP3 overexpression due to lack of MeCP2 may lead to delayed brain maturation.
Editor: Hagerstown, MD: American Association of Neuropathologists, Inc
Idioma: Inglês

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Methyl CpG-Binding Protein 2 (a Mutation of Which Causes Rett Syndrome) Directly Regulates Insulin-Like Growth Factor Binding Protein 3 in Mouse and Human Brains

Itoh, Masayuki ; Ide, Shuhei ; Takashima, Sachio ; Kudo, Shinichi ; Nomura, Yoshiko ; Segawa, Masaya ; Kubota, Takeo ; Mori, Hideo ; Tanaka, Shigeki ; Horie, Hiroshi ; Tanabe, Yuzo ; Goto, Yu-ichi

Hagerstown, MD: American Association of Neuropathologists, Inc

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