Gait analysis in a Mecp2 knockout mouse model of Rett syndrome reveals early-onset and progressive motor deficits.
Rett syndrome (RTT) is a genetic disorder characterized by a range of features including cognitive impairment, gait abnormalities and a reduction in purposeful hand skills. Mice harbouring knockout mutations in the Mecp2 gene display many RTT-like characteristics and are central to efforts to find novel therapies for the disorder. As hand stereotypies and gait abnormalities constitute major diagnostic criteria in RTT, it is clear that motor and gait-related phenotypes will be of importance in assessing preclinical therapeutic outcomes. We therefore aimed to assess gait properties over the prodromal phase in a functional knockout mouse model of RTT. In male Mecp2 knockout mice, we observed alterations in stride, coordination and balance parameters at 4 weeks of age, before the onset of other overt phenotypic changes as revealed by observational scoring. These data suggest that gait measures may be used as a robust and early marker of MeCP2-dysfunction in future preclinical therapeutic studies.
Institute of Neuroscience and Psychology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom; Pharmacology Department, Faculty of Medicine, Tanta University, Egypt.
Kamal K E
KK
Gadalla
Institute of Neuroscience and Psychology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom.
Paul D
PD
Ross
Institute of Neuroscience and Psychology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom.
John S
JS
Riddell
School of Life Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom.
Mark E S
ME
Bailey
Institute of Neuroscience and Psychology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom.
Stuart R
SR
Cobb
D000818:Animals; D004195:Disease Models, Animal; D020234:Gait Ataxia / Q000235:genetics / Q000503:physiopathology*; D008297:Male; D051783:Methyl-CpG-Binding Protein 2 / Q000172:deficiency*; D051379:Mice; D018345:Mice, Knockout; D000068079:Motor Disorders / Q000235:genetics / Q000503:physiopathology*; D015518:Rett Syndrome / Q000235:genetics / Q000503:physiopathology*
C497393:Mecp2 protein, mouse; D051783:Methyl-CpG-Binding Protein 2