MeCP2270 Mutant Protein Is Expressed in Astrocytes as well as in Neurons and Localizes in the Nucleus
| Autor: | Franco Laccone, H.Y. Agbemenyah, Ashraf U. Mannan, J.P. Arunachalam, Chiranjeevi Bodda, L.A. Kifayathullah |
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| Rok vydání: | 2010 |
| Předmět: |
Genetically modified mouse
Genetics congenital hereditary and neonatal diseases and abnormalities 0303 health sciences Rett syndrome Biology medicine.disease nervous system diseases MECP2 Xq28 03 medical and health sciences 0302 clinical medicine medicine.anatomical_structure Mutant protein mental disorders medicine MECP2 gene Molecular Biology Nucleus 030217 neurology & neurosurgery Genetics (clinical) 030304 developmental biology |
| Zdroj: | Cytogenetic and Genome Research. 129:290-297 |
| ISSN: | 1424-859X 1424-8581 |
| DOI: | 10.1159/000315906 |
| Popis: | The MECP2 gene, located at Xq28, encodes methyl-CpG-binding protein 2 (MeCP2), which is frequently mutated (up to 90%) in Rett syndrome (RTT). RTT is a progressive neurodevelopmental disorder, which affects primarily girls during early childhood and it is one of the most common causes of mental retardation in females. R270X is one of the most frequent recurrent MECP2 mutations among RTT cohorts. The R270X mutation resides within the TRD-NLS (Transcription Repression Domain-Nuclear Localization Signal) region of MeCP2 and causes a more severe clinical phenotype with increased mortality as compared to other mutations. To evaluate the functional role of the R270X mutation, we generated a transgenic mouse model expressing MeCP2270_EGFP (human mutation equivalent) by BAC recombineering. The expression pattern of MeCP2270_EGFP was similar to that of endogenous MeCP2. Strikingly, MeCP2270_EGFP localizes in the nucleus, contrary to the conjecture that R270X could cause disruption of the NLS. In primary hippocampal cells, we show that MeCP2270_EGFP was expressed in astrocytes by colocalization with the astrocyte-specific marker glial fibrillary acidic protein. Our data showing expression of MeCP2270_EGFP in transgenic mice astrocytes further reinforce the recent findings concerning the expression of MeCP2 in the glial cells. |
| Databáze: | OpenAIRE |
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