Research Awards

Mizue Hisano, Ph.D.
Lawrence Berkeley National Lab
Mentor: Terumi Kohwi-Shigematsu
Characterization of MeCP2-target genes in RTT
$100,000

Lay Final Report (November 2006)
This post-doctoral fellowship was transferred from Mizue Hisano to Masaru Miyano.

We studied higher-order chromatin structure at the Dlx5/6 locus and found change in the chromatin looping status in the Mecp2-null brain.  We are in the process of examining the effect of MECP2 ablation on expression of the Dlx gene family.  We have further examined the expression status of downstream candidate genes of Dlx5, and have identified Rxrg and Crabp1 to be dysregulated in the frontal cortex of Mecp2-null brains.  During the past two years, we have addressed the potential effect of Mecp2 mutation on muscle regeneration.  Muscle rigidity and reduced muscle mass are both known as typical symptoms of RTT patients. We focused on adult muscle progenitor cells, satellite cells, that are thought to represent the only population of committed myogenic progenitors in postnatal myogenesis. The result of this study suggests that muscle regeneration is impaired for Mecp2-null satellite cells which exhibit a defect in the myotube formation.  In adult Mecp2-null mice, substantially reduced numbers of activated satellite cells were detected upon injury when compared to wild-type mice.  We have several candidate genes, regulated by MECP2, that are responsible for these phenomena. Our data indicating that MECP2 plays a key role in satellite cell function predicts impaired postnatal myogenesis in Rett syndrome.