Gait Analysis in a Mecp2 Knockout Mouse Model of Rett Syndrome Reveals Early-Onset and Progressive Motor Deficits
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{"title"=>"Gait analysis in a Mecp2 knockout mouse model of rett syndrome reveals early-onset and progressive motor deficits", "type"=>"journal", "authors"=>[{"first_name"=>"Kamal K.E.", "last_name"=>"Gadalla", "scopus_author_id"=>"50261606400"}, {"first_name"=>"Paul D.", "last_name"=>"Ross", "scopus_author_id"=>"55363045600"}, {"first_name"=>"John S.", "last_name"=>"Riddell", "scopus_author_id"=>"7005596725"}, {"first_name"=>"Mark E.S.", "last_name"=>"Bailey", "scopus_author_id"=>"8896542700"}, {"first_name"=>"Stuart R.", "last_name"=>"Cobb", "scopus_author_id"=>"7102310116"}], "year"=>2014, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "scopus"=>"2-s2.0-84911875104", "pui"=>"600506793", "doi"=>"10.1371/journal.pone.0112889", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "sgr"=>"84911875104", "pmid"=>"25392929"}, "id"=>"0a349cca-9d13-3d11-9ebf-037c3a6a7e12", "abstract"=>"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.", "link"=>"http://www.mendeley.com/research/gait-analysis-mecp2-knockout-mouse-model-rett-syndrome-reveals-earlyonset-progressive-motor-deficits", "reader_count"=>20, "reader_count_by_academic_status"=>{"Researcher"=>8, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>7, "Other"=>1, "Student > Master"=>1, "Student > Bachelor"=>1, "Professor"=>1}, "reader_count_by_user_role"=>{"Researcher"=>8, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>7, "Other"=>1, "Student > Master"=>1, "Student > Bachelor"=>1, "Professor"=>1}, "reader_count_by_subject_area"=>{"Engineering"=>1, "Unspecified"=>1, "Nursing and Health Professions"=>1, "Agricultural and Biological Sciences"=>12, "Neuroscience"=>3, "Business, Management and Accounting"=>1, "Psychology"=>1}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Neuroscience"=>{"Neuroscience"=>3}, "Psychology"=>{"Psychology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>12}, "Nursing and Health Professions"=>{"Nursing and Health Professions"=>1}, "Business, Management and Accounting"=>{"Business, Management and Accounting"=>1}, "Unspecified"=>{"Unspecified"=>1}}, "group_count"=>0}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1792317"], "description"=>"<p>(A) Plot showing aggregate phenotype severity score (mean +/− SEM) in male wild-type (WT, black diamond symbols) and <i>Mecp2<sup>stop/y</sup></i> (grey circles) mice. <i>Mecp2<sup>stop/y</sup></i> mice show a gradual phenotype score progression that is significantly different from WT (WT n = 7; <i>Mecp2<sup>stop/y</sup></i> n = 8 at 3–7 weeks, n = 7 at week 8, n = 5 at week 9 and n = 4 at week 10); decreasing numbers of <i>Mecp2<sup>stop/y</sup></i> mice are explained by early death of some mutant mice. (B–F) Plots showing stride length, overlap distance, stance width, step angle and gait symmetry (mean +/− SEM) measured in WT and <i>Mecp2<sup>stop/y</sup></i> mice at 4, 8 and 10 weeks (WT n = 7 at 4 weeks and 5 at 8 & 10 weeks; <i>Mecp2<sup>stop/y</sup></i> n = 6 at 4 weeks, n = 5 at weeks 8 & 10. The treadmill speed was 25 cm/s. *<i>p</i><0.05 **<i>p</i><0.01 ***<i>p</i><0.001, Mann Whitney pairwise comparisons (A) and 2-way repeated measures ANOVA with Tukey <i>post hoc</i> pairwise comparisons (B–F).</p>", "links"=>[], "tags"=>["knockout mouse model", "Mecp 2 gene display", "rtt", "gait abnormalities", "disorder", "Mecp 2 knockout mice", "Mice harbouring knockout mutations", "Mecp 2 Knockout Mouse Model", "Progressive Motor Deficits Rett syndrome", "abnormality"], "article_id"=>1239805, "categories"=>["Biological Sciences", "Science Policy"], "users"=>["Kamal K. E. Gadalla", "Paul D. Ross", "John S. Riddell", "Mark E. S. Bailey", "Stuart R. Cobb"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0112889.g002", "stats"=>{"downloads"=>1, "page_views"=>24, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Automated_gait_analysis_reveals_early_signs_of_motor_defects_in_Mecp2_stop_y_mice_/1239805", "title"=>"Automated gait analysis reveals early signs of motor defects in <i>Mecp2<sup>stop/y</sup></i> mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-11-13 03:18:34"}
  • {"files"=>["https://ndownloader.figshare.com/files/1792315"], "description"=>"<p>(A) Video still image showing mouse walking on transparent treadmill (viewed from below) at 25 cm/s. (B) Placement of each paw is detected from the video illustrated in (A). (C) Graph of paw area in contact with the treadmill surface for each paw over time (one session, one animal); the area outlined in black has been replotted in (D). (D) Excerpt from (C) showing calculated paw area in contact with treadmill surface over time for a representative single paw (right fore; pink in B and C), from which multiple stride indices can be obtained (labeled). (E) Column plots showing stride time measures (mean +/− SEM) for each limb in 8 week old wild-type (WT) and <i>Mecp2<sup>stop/y</sup></i> mice (***<i>p</i><0.001 relative to WT; <i>t</i>-test, n = 5 per genotype).</p>", "links"=>[], "tags"=>["knockout mouse model", "Mecp 2 gene display", "rtt", "gait abnormalities", "disorder", "Mecp 2 knockout mice", "Mice harbouring knockout mutations", "Mecp 2 Knockout Mouse Model", "Progressive Motor Deficits Rett syndrome", "abnormality"], "article_id"=>1239803, "categories"=>["Biological Sciences", "Science Policy"], "users"=>["Kamal K. E. Gadalla", "Paul D. Ross", "John S. Riddell", "Mark E. S. Bailey", "Stuart R. Cobb"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0112889.g001", "stats"=>{"downloads"=>0, "page_views"=>25, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Treadmill_based_measurement_of_gait_properties_in_Mecp2_stop_y_mice_/1239803", "title"=>"Treadmill-based measurement of gait properties in <i>Mecp2<sup>stop/y</sup></i> mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-11-13 03:18:34"}

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Relative Metric

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