On November 20th, RSRF organized a Research Update featuring Dr. Huda Zoghbi of Baylor College of Medicine. To read a summary of Dr. Zoghbi's talk, please visit our website.

Monday, January 31st, is the deadline for the scientific community to seek funds from RSRF for their Rett Syndrome research projects. RSRF has aggressively advertised the availability of research grants and post-doctoral fellowships over the past few months. Researchers have been instructed to submit a letter of intent which briefly summarizes the proposed experiments. Our scientific advisory board will review all the proposals and short-list the ones that meet our criteria: scientific excellence of project, caliber of applicant, relevancy to Rett Syndrome. These applicants will be invited to submit a full grant application by the May 3rd deadline. Upon the recommendations of the scientific advisory board the RSRF Board of Trustees will vote on the 2005 Awards in July.

The Strollathon is the signature event of the RSRF. It is a fun-filled event which not only raises crucial research dollars but also increases public awareness of Rett Syndrome in your community.  Last year, Strollathon events were held in four cities across the country and raised over $450,000!

2005 promises to be the most successful Strollathon program ever.  Presently, seven events are being planned for this year.  Strollathons will be held this Spring in Connecticut, Pennsylvania and Massachussetts.  In addition, events are being coordinated in Washington, Virginia, Texas and Ohio.  Event Chairs and organizing committees are presently recruiting corporate sponsorships and Team Captains.   We encourage you to get involved and help raise much needed research dollars.  With your support, there is no doubt that we will see great success with each of Strollathon events.  For more information, please contact the Event Chairs below.

	Location			Date			Event Chair
	Harrisburg, PA		May 14		Kristy Kramer
	CT/NY/NJ		May 22		Monica Coenraads
	Cape Cod, MA		June 4		Jennifer and Justin Endres

Please be on the lookout for information on our Fall Strollathons -- coming soon!

The authors, who are funded by RSRF, investigate whether Rett Syndrome, autism and Angelman Syndrome may have genetic overlaps. Click here or on the title above to read the abstract and lay summary.

While epilepsy has long been thought to boost production of new brain cells (neurons) as a means of repairing injury, a new study shows that chronic seizures actually decrease new neuron production in the brain's learning and memory center. Click here to learn more.

Abstract
Autism is a common neurodevelopmental disorder of complex genetic etiology. Rett syndrome, an X-linked dominant disorder caused by MECP2 mutations, and Angelman syndrome, an imprinted disorder caused by maternal 15q11-13 or UBE3A deficiency, have phenotypic and genetic overlap with autism. MECP2 encodes methyl CpG binding protein 2 (MeCP2) that acts as a transcriptional repressor for methylated gene constructs, but is surprisingly not required for maintaining imprinted gene expression. Here we test the hypothesis that MECP2 deficiency may affect the level of expression of UBE3A and neighboring autism candidate gene GABRB3 without necessarily affecting imprinted expression. Multiple quantitative methods were used, including automated quantitation of immunofluorescence and in situ hybridization by laser scanning cytometry (LSC) on tissue microarrays, immunoblot, and TaqMan PCR. The results demonstrated significant defects in UBE3A/E6AP expression in two different Mecp2 deficient mouse strains and human Rett, Angelman, and autism brains compared to controls. Although no difference was observed in the allelic expression of several imprinted transcripts in Mecp2-null brain, Ube3a sense expression was significantly reduced, consistent with the decrease in protein. A nonimprinted gene from 15q11-13, GABRB3, encoding the beta3 subunit of the GABAA receptor, also showed significantly reduced expression in multiple Rett, Angelman, and autism brain samples, and Mecp2 deficient mice by quantitative immunoblot. These results suggest an overlapping pathway of gene dysregulation within 15q11-13 in Rett, Angelman, and autism, and implicate MeCP2 in the regulation of UBE3A and GABRB3 expression in the postnatal mammalian brain.

Lay Summary
We know that Rett Syndrome is caused by mutations in a gene called MECP2. Angelman Syndrome, a disorder with significant clinical overlaps with Rett is caused by mutations in the UBE3A gene. The genes involved in autism remain elusive but certain candidate areas have come to light including a section on chromosome 15 which contains a gene called GABRB3. Janine LaSalle and colleagues were interested in looking at levels of expression of the UBE3A and GABRB3 genes in tissue samples from MECP2 mutated mice or humans. Interestingly both genes showed significant defects in expression levels. A conclusion can be drawn that implicates MECP2 in the regulation of these 2 genes.