Tsix-Mecp2 female mouse model for Rett syndrome reveals that low-level MECP2 expression extends life and improves neuromotor function.

ABSTRACT: Rett syndrome (RTT) is a severe neurodevelopmental disorder caused by a mutation in the X-linked methyl-CpG-binding protein 2 (MECP2). There is currently no disease-specific treatment, but MECP2 restoration through reactivation of the inactive X (Xi) has been of considerable interest. Progress toward an Xi-reactivation therapy has been hampered by a lack of suitable female mouse models. Because of cellular mosaicism due to random X-chromosome inactivation (XCI), Mecp2^+/- heterozygous females develop only mild RTT. Here, we create an improved female mouse model by introducing a mutation in Tsix, the antisense regulator of XCI allelic choice. Tsix-Mecp2 mice show reduced MECP2 mosaicism and closely phenocopy the severely affected Mecp2-null males. Ts

SUBMITTER: Carrette LLG 

PROVIDER: S-EPMC6094149 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature