Human Molecular Genetics Advance Access published online on October 26, 2005
Human Molecular Genetics, doi:10.1093/hmg/ddi402
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1 The Neurosciences Institute, San Diego, California 92121, USA
* To whom correspondence should be addressed. Rett syndrome (RTT) is caused by mutations in the gene encoding methyl CpG-binding protein 2 (MeCP2). Although MeCP2 shows widespread expression in both neuronal and non-neuronal tissues, the symptoms of RTT are largely neurological. Herein, we have identified the regulatory region of the mouse Mecp2 gene that is sufficient for its restricted expression in neurons. A segment of the Mecp2 gene (-677/ + 56) exhibited strong promoter activity in neuronal cell lines and cortical neurons, but was inactive in non-neuronal cells and glia. The region necessary for neuronal-specific promoter activity was located within a 19 bp region (-63/-45). Several nuclear factors were found to bind to this region and some of these factors were enriched in nuclear extracts prepared from the brain. To examine the activity of the Mecp2 promoter in vivo, we generated transgenic mice expressing the LacZ reporter driven by the -677/ + 56 region of the Mecp2 gene. The transgene was expressed in the mesencephalon as early as E10, and in the hindbrain and spinal cord by E12. Interestingly, a marked induction of transgene expression was observed postnatally throughout the brain, similar to that of endogenous MeCP2. However, expression of the transgene was absent in non-neuronal tissues that are known to express Mecp2. Taken together, these data indicate that the -677/ + 56 region of the Mecp2 promoter partially recapitulates the native expression pattern of the Mecp2 gene, which possesses restricted expression in neurons of the central nervous system.
Received July 27, 2005
Revised October 1, 2005
Accepted October 18, 2005
Article
A Segment of the Mecp2 Promoter Is Sufficient to Drive Expression in Neurons
2 The Neurosciences Institute 10640 John Jay Hopkins Dr. San Diego, CA92121
Frederick S. Jones, E-mail: jones{at}nsi.edu
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