Fig. 1

Analysis of point mutations responsible for Rett syndrome (RTT) in human and mouse. a The primary protein structure of methyl-CpG-binding protein 2 (MeCP2), which is a chromosomal protein that binds to methylated DNA, highlights two key functional domains—a methyl-CpG-binding domain (MBD) and a NCoR/SMRT co-repressor interaction domain (NID). Shown as red vertical lines below the schematic are the positions of all RTT-causing missense mutations (RettBASE; http://mecp2.chw.edu.au/). The positions of three particular RTT-causing missense mutations—R133C, T158M and R306C, reflecting the spectrum of clinical severity—are indicated above the schematic (modified from [6]). b The approximate clinical severity of patients possessing the specific missense mutations T158M (red), R306C (blue) or R133C (green), based on independent studies using a variety of clinical severity score systems, for example [3]. c Scores of phenotypic severity of mouse models containing the T158M (red), R306C (blue) and R133C (green) missense mutations, in comparison with those of wild-type mice (dark gray solid line) and Mecp2-null mice (pale gray broken line). The asterisks indicate where no animals of that genotype survived beyond the indicated time-point. The data are adapted from Brown et al. [2] and are reproduced with permission of Oxford University Press