Select Page

D. BRUNNER1, P. A. KABITZKE, M. OSBORNE, A. BARBOZA, L. THIEDE, N. ROBERTS, T. HANANIA

X-linked MECP2 gene mutations in humans have been shown to be associated with loss of voluntary movements, including speech and hand movements. Male MECP2 homozygous mice are commonly used in preclinical studies and show a distinct phenotype but typically do not survive past 3 months of age and cannot perform many behavioral tests due to their compromised state. The female MECP2 Bird mouse (Mecp2tm1.1Bird) lacks one copy of the Mecp2 excised with Cre-loxP technology, has normal survival and appears quite healthy. However, we found that this model shows increased hindlimb clasping, weaker grip strength, and impaired ability to remain on the rotarod. The female Mecp2 Bird mouse also exhibits decreased acoustic startle response and decreased optokinetic response as measured by turning of the head in the direction of stripe movement, a measure of reflexive behavior and smooth eye tracking. In addition, female Bird mice reproduce the apnea type seen in Rett. Lastly, female Bird Rett mice from 6 weeks of age onward demonstrate a distinct gait phenotype as measured in PsychoGenics’ proprietary NeuroCube® System. This high- throughput system can quantitatively asses a disease phenotype, can quantify drug recovery, and has been validated in many drug discovery and screening studies. A novel model, the Mecp2 heterozygous rat (SAGE) showed similar gait deficits starting at 8 weeks of age, extending the availability of robust models of Rett with face validity.