MeCP2 in the enteric nervous system

• Published in: Neurogastroenterology and motility Vol. 27; no. 8; pp. 1156 - 1161
• Main Authors: Wahba, G., Schock, S. C., Claridge, E., Bettolli, M., Grynspan, D., Humphreys, P., Staines, W. A.
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.08.2015
• Subjects: Adolescent; Animals; Appendix - metabolism; Colon - metabolism; development; enteric nervous system; Enteric Nervous System - metabolism; Female; gastrointestinal dysmotility; gastrointestinal tract; Gastrointestinal Tract - metabolism; Humans; Intestine, Small - metabolism; Male; MeCP2; Methyl-CpG-Binding Protein 2 - metabolism; Mice; myenteric plexus; Neurons - metabolism; Rett syndrome; MeCP2; development; gastrointestinal dysmotility; gastrointestinal tract; Rett syndrome; enteric nervous system; myenteric plexus
• ISSN: 1350-1925; 1365-2982
• DOI: 10.1111/nmo.12605

Background Rett syndrome (RTT) is an intellectual deficit and movement disorder that develops during early childhood in girls. Affected children are normal until 6–18 months of age, after which symptoms begin to appear. Most cases of RTT are due to mutations in the MeCP2 gene leading to disruption of neuronal communication in the central nervous system. In addition, RTT patients show peripheral ailments such as gastrointestinal (GI), respiratory, and cardiac dysfunction. The etiology of intestinal dysfunction in RTT is not well‐understood. Reports on the presence of MeCP2 in the peripheral nervous system are scant. As such we examined the levels of MeCP2 in human and murine GI tissue and assessed MeCP2 expression at various developmental stages. Methods Immunohistochemistry for MeCP2, HuC/D, juvenile beta tubulin, and GFAP was performed on human and murine intestine. Western blots of these same tissues were probed with MeCP2, vAChT, nNOS, and beta‐actin antibodies. Key Results MeCP2 is expressed throughout the GI tract. MeCP2 is expressed specifically in the enteric nervous system of the GI tract. MeCP2 is expressed in the GI tract throughout development with appearance beginning at or before E11.5 in the murine intestine. Conclusions & Inferences The proof of MeCP2 expression in enteric neurons suggests that the GI dysmotility in Rett may arise from enteric network dysfunction secondary to MeCP2 mutation. This study aimed to investigate if MeCP2 is expressed in the human and murine ENS and at which stages of development it first appears. MeCP2 is expressed throughout development of the GI tract with appearance at or before E11.5 in mice, specifically in the enteric nervous tissue. This study opens the possibility for treatment of the GI dysfunction in Rett syndrome with peripheral acting drugs and growth factors.