Rett Disorder

X-linked methyl CpG binding protein 2 (MECP2) gene mutations in humans have been shown to result in Rett syndrome, a leading cause of intellectual disabilities in girls and associated with embryonic lethality in males (Silva and Ehninger, 2009, Ricciardi et al., 2011, Goffin et al., 2012). Symptoms include the loss of voluntary movements, including speech and hand movements, gait disturbances, autism, and disorganized breathing patterns (Guy et al., 2001).

The female MECP2 Bird mouse (Mecp2tm1.1Bird) lacks one copy of the Mecp2 excised with Cre-loxP technology, has normal survival, appears quite healthy, and is a medically-relevant model (Chen et al., 2001).

Female Mecp2 mice show robust deficits amenable to drug screening of compounds that could be beneficial in the treatment of Rett Syndrome. These deficits appear in measures of gait, respiration, motor coordination, sensory-motor gating, and emerge as early as 6 weeks of age for some measures. Brain-derived neurotrophic factor (BDNF) and BDNF isoforms in the cortex are reduced in female Mecp2 mice at 16 weeks of age. Importantly, the behavioral and molecular characteristics of this model recapitulate the pathology and functional deficits found in Rett syndrome, even reaching a plateau consistent with clinical observations (Ogier et al., 2007, Stearns et al., 2007, Abdala et al., 2010). Considering the strong construct and etiological validity of the models and the robustness of the deficits, a drug screen using female Mecp2 rodents provides strong translation to the clinic.

Rett Disorder

Rett Disorder

Rett Disorder Rett Disorder Rett Disorder Rett Disorder Rett Disorder

Rett Disorder Rett Disorder Rett Disorder

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