Comprehensive Behavioral and Molecular Characterization of a New Knock-In Mouse Model of Huntington’s Disease: zQ175
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{"title"=>"Comprehensive Behavioral and Molecular Characterization of a New Knock-In Mouse Model of Huntington's Disease: ZQ175", "type"=>"journal", "authors"=>[{"first_name"=>"Liliana B.", "last_name"=>"Menalled", "scopus_author_id"=>"6508319317"}, {"first_name"=>"Andrea E.", "last_name"=>"Kudwa", "scopus_author_id"=>"6505987637"}, {"first_name"=>"Sam", "last_name"=>"Miller", "scopus_author_id"=>"7406290363"}, {"first_name"=>"Jon", "last_name"=>"Fitzpatrick", "scopus_author_id"=>"55233552600"}, {"first_name"=>"Judy", "last_name"=>"Watson-Johnson", "scopus_author_id"=>"8749707000"}, {"first_name"=>"Nicole", "last_name"=>"Keating", "scopus_author_id"=>"55534300800"}, {"first_name"=>"Melinda", "last_name"=>"Ruiz", "scopus_author_id"=>"55534756300"}, {"first_name"=>"Richard", "last_name"=>"Mushlin", "scopus_author_id"=>"6602391474"}, {"first_name"=>"William", "last_name"=>"Alosio", "scopus_author_id"=>"55534262300"}, {"first_name"=>"Kristi", "last_name"=>"McConnell", "scopus_author_id"=>"55534172800"}, {"first_name"=>"David", "last_name"=>"Connor", "scopus_author_id"=>"55389191700"}, {"first_name"=>"Carol", "last_name"=>"Murphy", "scopus_author_id"=>"56891830200"}, {"first_name"=>"Steve", "last_name"=>"Oakeshott", "scopus_author_id"=>"55582040600"}, {"first_name"=>"Mei", "last_name"=>"Kwan", "scopus_author_id"=>"55535001600"}, {"first_name"=>"Jose", "last_name"=>"Beltran", "scopus_author_id"=>"55317698800"}, {"first_name"=>"Afshin", "last_name"=>"Ghavami", "scopus_author_id"=>"6603355137"}, {"first_name"=>"Dani", "last_name"=>"Brunner", "scopus_author_id"=>"16218210300"}, {"first_name"=>"Larry C.", "last_name"=>"Park", "scopus_author_id"=>"37002099300"}, {"first_name"=>"Sylvie", "last_name"=>"Ramboz", "scopus_author_id"=>"6602779850"}, {"first_name"=>"David", "last_name"=>"Howland", "scopus_author_id"=>"7003562939"}], "year"=>2012, "source"=>"PLoS ONE", "identifiers"=>{"pui"=>"366319145", "sgr"=>"84871422859", "pmid"=>"23284626", "scopus"=>"2-s2.0-84871422859", "isbn"=>"1932-6203", "doi"=>"10.1371/journal.pone.0049838", "issn"=>"19326203"}, "id"=>"ed76d453-9674-39d0-8f47-d9e1544d0faa", "abstract"=>"Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder characterized by motor, cognitive and psychiatric manifestations. Since the mutation responsible for the disease was identified as an unstable expansion of CAG repeats in the gene encoding the huntingtin protein in 1993, numerous mouse models of HD have been generated to study disease pathogenesis and evaluate potential therapeutic approaches. Of these, knock-in models best mimic the human condition from a genetic perspective since they express the mutation in the appropriate genetic and protein context. Behaviorally, however, while some abnormal phenotypes have been detected in knock-in mouse models, a model with an earlier and more robust phenotype than the existing models is required. We describe here for the first time a new mouse line, the zQ175 knock-in mouse, derived from a spontaneous expansion of the CAG copy number in our CAG 140 knock-in colony [1]. Given the inverse relationship typically observed between age of HD onset and length of CAG repeat, since this new mouse line carries a significantly higher CAG repeat length it was expected to be more significantly impaired than the parent line. Using a battery of behavioral tests we evaluated both heterozygous and homozygous zQ175 mice. Homozygous mice showed motor and grip strength abnormalities with an early onset (8 and 4 weeks of age, respectively), which were followed by deficits in rotarod and climbing activity at 30 weeks of age and by cognitive deficits at around 1 year of age. Of particular interest for translational work, we also found clear behavioral deficits in heterozygous mice from around 4.5 months of age, especially in the dark phase of the diurnal cycle. Decreased body weight was observed in both heterozygotes and homozygotes, along with significantly reduced survival in the homozygotes. In addition, we detected an early and significant decrease of striatal gene markers from 12 weeks of age. These data suggest that the zQ175 knock-in line could be a suitable model for the evaluation of therapeutic approaches and early events in the pathogenesis of HD.", "link"=>"http://www.mendeley.com/research/comprehensive-behavioral-molecular-characterization-new-knockin-mouse-model-huntingtons-disease-zq17-2", "reader_count"=>94, "reader_count_by_academic_status"=>{"Unspecified"=>2, "Professor > Associate Professor"=>1, "Researcher"=>31, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>23, "Student > Postgraduate"=>4, "Student > Master"=>15, "Other"=>3, "Student > Bachelor"=>11, "Professor"=>2}, "reader_count_by_user_role"=>{"Unspecified"=>2, "Professor > Associate Professor"=>1, "Researcher"=>31, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>23, "Student > Postgraduate"=>4, "Student > Master"=>15, "Other"=>3, "Student > Bachelor"=>11, "Professor"=>2}, "reader_count_by_subject_area"=>{"Unspecified"=>5, "Biochemistry, Genetics and Molecular Biology"=>5, "Agricultural and Biological Sciences"=>43, "Medicine and Dentistry"=>8, "Neuroscience"=>25, "Arts and Humanities"=>1, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Psychology"=>6}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>8}, "Neuroscience"=>{"Neuroscience"=>25}, "Psychology"=>{"Psychology"=>6}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>43}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>5}, "Unspecified"=>{"Unspecified"=>5}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}, "Arts and Humanities"=>{"Arts and Humanities"=>1}}, "reader_count_by_country"=>{"Austria"=>2, "United States"=>5, "Denmark"=>1, "United Kingdom"=>1, "Portugal"=>1}, "group_count"=>7}

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  • {"files"=>["https://ndownloader.figshare.com/files/520197"], "description"=>"<p>Proportion of mice climbing in the rearing climbing assay in the wild type, heterozygous and homozygous group during the dark phase of the diurnal cycle.</p>", "links"=>[], "tags"=>["mice", "climbing", "rearing", "assay", "heterozygous", "homozygous", "diurnal"], "article_id"=>190665, "categories"=>["Biological Sciences", "Genetics", "Neuroscience"], "users"=>["Liliana B. Menalled", "Andrea E. Kudwa", "Sam Miller", "Jon Fitzpatrick", "Judy Watson-Johnson", "Nicole Keating", "Melinda Ruiz", "Richard Mushlin", "William Alosio", "Kristi McConnell", "David Connor", "Carol Murphy", "Steve Oakeshott", "Mei Kwan", "Jose Beltran", "Afshin Ghavami", "Dani Brunner", "Larry C. Park", "Sylvie Ramboz", "David Howland"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0049838.g007", "stats"=>{"downloads"=>1, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Proportion_of_mice_climbing_in_the_rearing_climbing_assay_in_the_wild_type_heterozygous_and_homozygous_group_during_the_dark_phase_of_the_diurnal_cycle_/190665", "title"=>"Proportion of mice climbing in the rearing climbing assay in the wild type, heterozygous and homozygous group during the dark phase of the diurnal cycle.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-12-20 00:11:05"}
  • {"files"=>["https://ndownloader.figshare.com/files/520109"], "description"=>"<p>Grip strength (mean ± SEM) of wild type, heterozygous and homozygous mice as a function of age during the light phase of the diurnal cycle.</p>", "links"=>[], "tags"=>["heterozygous", "homozygous", "mice", "diurnal"], "article_id"=>190571, "categories"=>["Biological Sciences", "Genetics", "Neuroscience"], "users"=>["Liliana B. Menalled", "Andrea E. Kudwa", "Sam Miller", "Jon Fitzpatrick", "Judy Watson-Johnson", "Nicole Keating", "Melinda Ruiz", "Richard Mushlin", "William Alosio", "Kristi McConnell", "David Connor", "Carol Murphy", "Steve Oakeshott", "Mei Kwan", "Jose Beltran", "Afshin Ghavami", "Dani Brunner", "Larry C. Park", "Sylvie Ramboz", "David Howland"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0049838.g006", "stats"=>{"downloads"=>1, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Grip_strength_mean_177_SEM_of_wild_type_heterozygous_and_homozygous_mice_as_a_function_of_age_during_the_light_phase_of_the_diurnal_cycle_/190571", "title"=>"Grip strength (mean ± SEM) of wild type, heterozygous and homozygous mice as a function of age during the light phase of the diurnal cycle.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-12-20 00:09:31"}
  • {"files"=>["https://ndownloader.figshare.com/files/520802"], "description"=>"<p>Test ages for behavioral work, broken down by test cohort.</p>", "links"=>[], "tags"=>["ages"], "article_id"=>191276, "categories"=>["Biological Sciences", "Genetics", "Neuroscience"], "users"=>["Liliana B. Menalled", "Andrea E. Kudwa", "Sam Miller", "Jon Fitzpatrick", "Judy Watson-Johnson", "Nicole Keating", "Melinda Ruiz", "Richard Mushlin", "William Alosio", "Kristi McConnell", "David Connor", "Carol Murphy", "Steve Oakeshott", "Mei Kwan", "Jose Beltran", "Afshin Ghavami", "Dani Brunner", "Larry C. Park", "Sylvie Ramboz", "David Howland"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0049838.t001", "stats"=>{"downloads"=>1, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Test_ages_for_behavioral_work_broken_down_by_test_cohort_/191276", "title"=>"Test ages for behavioral work, broken down by test cohort.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-12-20 00:21:16"}
  • {"files"=>["https://ndownloader.figshare.com/files/520740"], "description"=>"<p>Qualitative Polymerase Chain Reaction (qPCR) information.</p>", "links"=>[], "tags"=>["polymerase"], "article_id"=>191213, "categories"=>["Biological Sciences", "Genetics", "Neuroscience"], "users"=>["Liliana B. Menalled", "Andrea E. Kudwa", "Sam Miller", "Jon Fitzpatrick", "Judy Watson-Johnson", "Nicole Keating", "Melinda Ruiz", "Richard Mushlin", "William Alosio", "Kristi McConnell", "David Connor", "Carol Murphy", "Steve Oakeshott", "Mei Kwan", "Jose Beltran", "Afshin Ghavami", "Dani Brunner", "Larry C. Park", "Sylvie Ramboz", "David Howland"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0049838.t002", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Qualitative_Polymerase_Chain_Reaction_qPCR_information_/191213", "title"=>"Qualitative Polymerase Chain Reaction (qPCR) information.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-12-20 00:20:13"}
  • {"files"=>["https://ndownloader.figshare.com/files/519757"], "description"=>"<p>Kaplan-Meier survival curve in WT vs. homozygous mice as a function of genotype and age.</p>", "links"=>[], "tags"=>["wt", "homozygous", "mice", "genotype"], "article_id"=>190226, "categories"=>["Biological Sciences", "Genetics", "Neuroscience"], "users"=>["Liliana B. Menalled", "Andrea E. Kudwa", "Sam Miller", "Jon Fitzpatrick", "Judy Watson-Johnson", "Nicole Keating", "Melinda Ruiz", "Richard Mushlin", "William Alosio", "Kristi McConnell", "David Connor", "Carol Murphy", "Steve Oakeshott", "Mei Kwan", "Jose Beltran", "Afshin Ghavami", "Dani Brunner", "Larry C. Park", "Sylvie Ramboz", "David Howland"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0049838.g002", "stats"=>{"downloads"=>3, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Kaplan_Meier_survival_curve_in_WT_vs_homozygous_mice_as_a_function_of_genotype_and_age_/190226", "title"=>"Kaplan-Meier survival curve in WT vs. homozygous mice as a function of genotype and age.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-12-20 00:03:46"}
  • {"files"=>["https://ndownloader.figshare.com/files/520605"], "description"=>"<p>Relative mRNA levels are normalized to age matched and gender matched wild type controls. For normalization, the geometric mean of UBbc, Eif4a2 and ATP5B was used. Gender separation was performed with the 12 and 41 week groups. *, p<0.05; **, p<0.01; ***, p<0.001. The number on each bar graph represents “n” for each group.</p>", "links"=>[], "tags"=>["striatal", "mrna", "wildtype", "heterozyous", "homozygous", "zq175", "mice", "18", "41", "weeks"], "article_id"=>191059, "categories"=>["Biological Sciences", "Genetics", "Neuroscience"], "users"=>["Liliana B. Menalled", "Andrea E. Kudwa", "Sam Miller", "Jon Fitzpatrick", "Judy Watson-Johnson", "Nicole Keating", "Melinda Ruiz", "Richard Mushlin", "William Alosio", "Kristi McConnell", "David Connor", "Carol Murphy", "Steve Oakeshott", "Mei Kwan", "Jose Beltran", "Afshin Ghavami", "Dani Brunner", "Larry C. Park", "Sylvie Ramboz", "David Howland"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0049838.g011", "stats"=>{"downloads"=>1, "page_views"=>27, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_relative_striatal_mRNA_expression_level_of_wildtype_WT_heterozyous_HET_and_homozygous_HOMO_zQ175_mice_at_12_18_and_41_weeks_of_age_analyzed_by_qPCR_/191059", "title"=>"The relative striatal mRNA expression level of wildtype (WT), heterozyous (HET) and homozygous (HOMO) zQ175 mice at 12, 18 and 41 weeks of age, analyzed by qPCR.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-12-20 00:17:39"}
  • {"files"=>["https://ndownloader.figshare.com/files/281197", "https://ndownloader.figshare.com/files/281277", "https://ndownloader.figshare.com/files/281337", "https://ndownloader.figshare.com/files/281386", "https://ndownloader.figshare.com/files/281428", "https://ndownloader.figshare.com/files/281510", "https://ndownloader.figshare.com/files/281583"], "description"=>"<div><p>Huntington’s disease (HD) is an autosomal dominant neurodegenerative disorder characterized by motor, cognitive and psychiatric manifestations. Since the mutation responsible for the disease was identified as an unstable expansion of CAG repeats in the gene encoding the huntingtin protein in 1993, numerous mouse models of HD have been generated to study disease pathogenesis and evaluate potential therapeutic approaches. Of these, knock-in models best mimic the human condition from a genetic perspective since they express the mutation in the appropriate genetic and protein context. Behaviorally, however, while some abnormal phenotypes have been detected in knock-in mouse models, a model with an earlier and more robust phenotype than the existing models is required. We describe here for the first time a new mouse line, the zQ175 knock-in mouse, derived from a spontaneous expansion of the CAG copy number in our CAG 140 knock-in colony <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0049838#pone.0049838-Menalled1\">[1]</a>. Given the inverse relationship typically observed between age of HD onset and length of CAG repeat, since this new mouse line carries a significantly higher CAG repeat length it was expected to be more significantly impaired than the parent line. Using a battery of behavioral tests we evaluated both heterozygous and homozygous zQ175 mice. Homozygous mice showed motor and grip strength abnormalities with an early onset (8 and 4 weeks of age, respectively), which were followed by deficits in rotarod and climbing activity at 30 weeks of age and by cognitive deficits at around 1 year of age. Of particular interest for translational work, we also found clear behavioral deficits in heterozygous mice from around 4.5 months of age, especially in the dark phase of the diurnal cycle. Decreased body weight was observed in both heterozygotes and homozygotes, along with significantly reduced survival in the homozygotes. In addition, we detected an early and significant decrease of striatal gene markers from 12 weeks of age. These data suggest that the zQ175 knock-in line could be a suitable model for the evaluation of therapeutic approaches and early events in the pathogenesis of HD.</p> </div>", "links"=>[], "tags"=>["molecular", "characterization", "knock-in", "zq175"], "article_id"=>115448, "categories"=>["Biological Sciences", "Genetics", "Neuroscience"], "users"=>["Liliana B. Menalled", "Andrea E. Kudwa", "Sam Miller", "Jon Fitzpatrick", "Judy Watson-Johnson", "Nicole Keating", "Melinda Ruiz", "Richard Mushlin", "William Alosio", "Kristi McConnell", "David Connor", "Carol Murphy", "Steve Oakeshott", "Mei Kwan", "Jose Beltran", "Afshin Ghavami", "Dani Brunner", "Larry C. Park", "Sylvie Ramboz", "David Howland"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0049838.s001", "https://dx.doi.org/10.1371/journal.pone.0049838.s002", "https://dx.doi.org/10.1371/journal.pone.0049838.s003", "https://dx.doi.org/10.1371/journal.pone.0049838.s004", "https://dx.doi.org/10.1371/journal.pone.0049838.s005", "https://dx.doi.org/10.1371/journal.pone.0049838.s006", "https://dx.doi.org/10.1371/journal.pone.0049838.s007"], "stats"=>{"downloads"=>53, "page_views"=>17, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Comprehensive_Behavioral_and_Molecular_Characterization_of_a_New_Knock_In_Mouse_Model_of_Huntington_s_Disease_zQ175__/115448", "title"=>"Comprehensive Behavioral and Molecular Characterization of a New Knock-In Mouse Model of Huntington’s Disease: zQ175", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2012-12-20 01:30:48"}
  • {"files"=>["https://ndownloader.figshare.com/files/520021"], "description"=>"<p>Latency to fall from the rotarod (mean ± SEM) of wild type, heterozygous and homozygous mice as a function of age during the dark phase of the diurnal cycle.</p>", "links"=>[], "tags"=>["rotarod", "heterozygous", "homozygous", "mice", "diurnal"], "article_id"=>190490, "categories"=>["Biological Sciences", "Genetics", "Neuroscience"], "users"=>["Liliana B. Menalled", "Andrea E. Kudwa", "Sam Miller", "Jon Fitzpatrick", "Judy Watson-Johnson", "Nicole Keating", "Melinda Ruiz", "Richard Mushlin", "William Alosio", "Kristi McConnell", "David Connor", "Carol Murphy", "Steve Oakeshott", "Mei Kwan", "Jose Beltran", "Afshin Ghavami", "Dani Brunner", "Larry C. Park", "Sylvie Ramboz", "David Howland"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0049838.g005", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Latency_to_fall_from_the_rotarod_mean_177_SEM_of_wild_type_heterozygous_and_homozygous_mice_as_a_function_of_age_during_the_dark_phase_of_the_diurnal_cycle_/190490", "title"=>"Latency to fall from the rotarod (mean ± SEM) of wild type, heterozygous and homozygous mice as a function of age during the dark phase of the diurnal cycle.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-12-20 00:08:10"}
  • {"files"=>["https://ndownloader.figshare.com/files/519668"], "description"=>"<p>Body weight (mean ± SEM) of wild type, heterozygous and homozygous mice as a function of age for female (A) and male (B) mice.</p>", "links"=>[], "tags"=>["heterozygous", "homozygous", "mice"], "article_id"=>190139, "categories"=>["Biological Sciences", "Genetics", "Neuroscience"], "users"=>["Liliana B. Menalled", "Andrea E. Kudwa", "Sam Miller", "Jon Fitzpatrick", "Judy Watson-Johnson", "Nicole Keating", "Melinda Ruiz", "Richard Mushlin", "William Alosio", "Kristi McConnell", "David Connor", "Carol Murphy", "Steve Oakeshott", "Mei Kwan", "Jose Beltran", "Afshin Ghavami", "Dani Brunner", "Larry C. Park", "Sylvie Ramboz", "David Howland"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0049838.g001", "stats"=>{"downloads"=>0, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Body_weight_mean_177_SEM_of_wild_type_heterozygous_and_homozygous_mice_as_a_function_of_age_for_female_A_and_male_B_mice_/190139", "title"=>"Body weight (mean ± SEM) of wild type, heterozygous and homozygous mice as a function of age for female (A) and male (B) mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-12-20 00:02:19"}
  • {"files"=>["https://ndownloader.figshare.com/files/520492"], "description"=>"<p>Overall visit frequency during PhenoCube testing at 37 weeks, broken down into 1 hour bins (A) and summarized across the two complete light/dark periods from lights-on on day 2 (B).</p>", "links"=>[], "tags"=>["phenocube", "37", "bins", "summarized", "periods", "lights-on"], "article_id"=>190956, "categories"=>["Biological Sciences", "Genetics", "Neuroscience"], "users"=>["Liliana B. Menalled", "Andrea E. Kudwa", "Sam Miller", "Jon Fitzpatrick", "Judy Watson-Johnson", "Nicole Keating", "Melinda Ruiz", "Richard Mushlin", "William Alosio", "Kristi McConnell", "David Connor", "Carol Murphy", "Steve Oakeshott", "Mei Kwan", "Jose Beltran", "Afshin Ghavami", "Dani Brunner", "Larry C. Park", "Sylvie Ramboz", "David Howland"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0049838.g010", "stats"=>{"downloads"=>1, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Overall_visit_frequency_during_PhenoCube_testing_at_37_weeks_broken_down_into_1_hour_bins_A_and_summarized_across_the_two_complete_light_dark_periods_from_lights_on_on_day_2_B_/190956", "title"=>"Overall visit frequency during PhenoCube testing at 37 weeks, broken down into 1 hour bins (A) and summarized across the two complete light/dark periods from lights-on on day 2 (B).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-12-20 00:15:56"}
  • {"files"=>["https://ndownloader.figshare.com/files/519839"], "description"=>"<p>Total distance covered in the Open Field per 5 minute bin (mean ± SEM) of wild type, heterozygous and homozygous mice as a function of age and test time during the dark phase of the diurnal cycle.</p>", "links"=>[], "tags"=>["covered", "bin", "heterozygous", "homozygous", "mice", "diurnal"], "article_id"=>190302, "categories"=>["Biological Sciences", "Genetics", "Neuroscience"], "users"=>["Liliana B. Menalled", "Andrea E. Kudwa", "Sam Miller", "Jon Fitzpatrick", "Judy Watson-Johnson", "Nicole Keating", "Melinda Ruiz", "Richard Mushlin", "William Alosio", "Kristi McConnell", "David Connor", "Carol Murphy", "Steve Oakeshott", "Mei Kwan", "Jose Beltran", "Afshin Ghavami", "Dani Brunner", "Larry C. Park", "Sylvie Ramboz", "David Howland"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0049838.g003", "stats"=>{"downloads"=>0, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Total_distance_covered_in_the_Open_Field_per_5_minute_bin_mean_177_SEM_of_wild_type_heterozygous_and_homozygous_mice_as_a_function_of_age_and_test_time_during_the_dark_phase_of_the_diurnal_cycle_/190302", "title"=>"Total distance covered in the Open Field per 5 minute bin (mean ± SEM) of wild type, heterozygous and homozygous mice as a function of age and test time during the dark phase of the diurnal cycle.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-12-20 00:05:02"}

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