MeCP2 R168X male and female mutant mice exhibit Rett-like behavioral deficits.

Area of Science:

• Neuroscience
• Genetics
• Developmental Biology

Background:

• Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutations in the methyl-CpG-binding protein 2 (MeCP2) gene.
• Most RTT cases stem from over 200 MeCP2 mutations, with limited characterization of behavioral phenotypes in existing mouse models, particularly females.

Purpose of the Study:

• To thoroughly phenotype male and female mice with the common MeCP2 R168X mutation.
• To compare the R168X mutant phenotypes with Mecp2 null mutants.
• To identify robust behavioral paradigms for preclinical trials in Rett syndrome.

Main Methods:

• Behavioral characterization of male and female mice carrying the MeCP2 R168X mutation.
• Comparison of R168X mutant phenotypes to Mecp2 null mutants.
• Assessment of motor function, cognitive function, anxiety, and seizure activity.

Main Results:

• MeCP2 R168X mutants exhibit core Rett syndrome features, including motor and cognitive deficits.
• Male R168X mutants display phenotypes similar to Mecp2 null males, with reduced anxiety.
• Female R168X mutants show a milder, later-onset phenotype than null females, with some seizures observed.

Conclusions:

• The MeCP2 R168X mouse model effectively mirrors clinical Rett syndrome features.
• Phenotypic differences between R168X and null female mice highlight the importance of model selection.
• Robust behavioral paradigms are identified, emphasizing the inclusion of female mice in preclinical studies for Rett syndrome.