Non-Motor and Motor Features in LRRK2 Transgenic Mice
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{"title"=>"Non-Motor and Motor Features in LRRK2 Transgenic Mice", "type"=>"journal", "authors"=>[{"first_name"=>"Zoë", "last_name"=>"Bichler", "scopus_author_id"=>"8771190900"}, {"first_name"=>"Han Chi", "last_name"=>"Lim", "scopus_author_id"=>"55806170900"}, {"first_name"=>"Li", "last_name"=>"Zeng", "scopus_author_id"=>"55383991100"}, {"first_name"=>"Eng King", "last_name"=>"Tan", "scopus_author_id"=>"7402263993"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"pui"=>"369443217", "sgr"=>"84880789550", "issn"=>"19326203", "pmid"=>"23936174", "scopus"=>"2-s2.0-84880789550", "doi"=>"10.1371/journal.pone.0070249", "isbn"=>"1932-6203"}, "id"=>"7cb4882e-50aa-3741-a131-bf53cc488f7a", "abstract"=>"BACKGROUND: Non-motor symptoms are increasingly recognized as important features of Parkinson's disease (PD). LRRK2 mutations are common causes of familial and sporadic PD. Non-motor features have not been yet comprehensively evaluated in LRRK2 transgenic mouse models. OBJECTIVE: Using a transgenic mouse model overexpressing the R1441G mutation of the human LRRK2 gene, we have investigated the longitudinal correlation between motor and non-motor symptoms and determined if specific non-motor phenotypes precede motor symptoms. METHODOLOGY: We investigated the onset of motor and non-motor phenotypes on the LRRK2(R1441G) BAC transgenic mice and their littermate controls from 4 to 21 month-old using a battery of behavioral tests. The transgenic mutant mice displayed mild hypokinesia in the open field from 16 months old, with gastrointestinal dysfunctions beginning at 6 months old. Non-motor features such as depression and anxiety-like behaviors, sensorial functions (pain sensitivity and olfaction), and learning and memory abilities in the passive avoidance test were similar in the transgenic animals compared to littermate controls. CONCLUSIONS: LRRK2(R1441G) BAC transgenic mice displayed gastrointestinal dysfunction at an early stage but did not have abnormalities in fine behaviors, olfaction, pain sensitivity, mood disorders and learning and memory compared to non-transgenic littermate controls. The observations on olfaction and gastrointestinal dysfunction in this model validate findings in human carriers. These mice did recapitulate mild Parkinsonian motor features at late stages but compensatory mechanisms modulating the progression of PD in these models should be further evaluated.", "link"=>"http://www.mendeley.com/research/nonmotor-motor-features-lrrk2-transgenic-mice", "reader_count"=>41, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Student > Doctoral Student"=>4, "Researcher"=>16, "Student > Ph. D. Student"=>11, "Student > Postgraduate"=>1, "Student > Master"=>2, "Other"=>1, "Student > Bachelor"=>3, "Lecturer"=>2}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Student > Doctoral Student"=>4, "Researcher"=>16, "Student > Ph. D. Student"=>11, "Student > Postgraduate"=>1, "Student > Master"=>2, "Other"=>1, "Student > Bachelor"=>3, "Lecturer"=>2}, "reader_count_by_subject_area"=>{"Unspecified"=>3, "Engineering"=>1, "Biochemistry, Genetics and Molecular Biology"=>3, "Medicine and Dentistry"=>8, "Agricultural and Biological Sciences"=>18, "Neuroscience"=>4, "Chemistry"=>1, "Psychology"=>2, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>8}, "Neuroscience"=>{"Neuroscience"=>4}, "Chemistry"=>{"Chemistry"=>1}, "Psychology"=>{"Psychology"=>2}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>18}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>3}, "Unspecified"=>{"Unspecified"=>3}}, "reader_count_by_country"=>{"United Kingdom"=>2}, "group_count"=>5}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1137512"], "description"=>"<p><b>A.</b> Number of rearing in the cylinder test. <b>B.</b> Latency to fall in the accelerated rotarod paradigm. <b>C.</b> Mean latency of staying gripped to the grid of a reverted cage lid. <b>D.</b> General activity in the open field test in a 15 min test: rearing (a), horizontal activity (b), activity in the center of the apparatus (c), and total number of fine activities (d). Data are means ± SEM, number of animals are indicated in the corresponding bar of the histogram. *p<0.05, **p<0.01, ***p<0.001 with MANOVA followed by post-hoc comparison (Bonferroni), and Student t test for single comparisons or Welch’s t test when variances were unequal.</p>", "links"=>[], "tags"=>["genetics", "Animal genetics", "Model organisms", "Animal models", "mouse", "neuroscience", "Behavioral neuroscience", "Motor systems", "Clinical research design", "Animal models of disease", "Mental health", "psychiatry", "Mood disorders", "Neuropsychiatric disorders", "neurology", "Parkinson disease", "abilities", "bac", "tg", "ntg", "mice"], "article_id"=>760160, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Zoë Bichler", "Han Chi Lim", "Li Zeng", "Eng King Tan"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0070249.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Motor_abilities_of_the_BAC_LRRK2_R1441G_Tg_and_NTg_mice_with_age_/760160", "title"=>"Motor abilities of the BAC <i>LRRK2<sup>R1441G</sup></i> Tg and NTg mice with age.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-07-30 11:12:39"}
  • {"files"=>["https://ndownloader.figshare.com/files/1137513"], "description"=>"<p>Horizontal, vertical and fine activity as well as total activity in the center of the arena, of mice at 6, 12, 16 and 20 months old. These results come from the experiments shown in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0070249#pone-0070249-g001\" target=\"_blank\">Figure 1</a> but expressed in 3 min intervals. Data are means ± SEM. *p<0.05, **p<0.01, ***p<0.001, with Welch’s t test within two values of the graph, MANOVA test analysis with “genotype” and “intervals” as factors when considering the genotype effect.</p>", "links"=>[], "tags"=>["genetics", "Animal genetics", "Model organisms", "Animal models", "mouse", "neuroscience", "Behavioral neuroscience", "Motor systems", "Clinical research design", "Animal models of disease", "Mental health", "psychiatry", "Mood disorders", "Neuropsychiatric disorders", "neurology", "Parkinson disease", "min", "intervals", "15"], "article_id"=>760161, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Zoë Bichler", "Han Chi Lim", "Li Zeng", "Eng King Tan"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0070249.g002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Activity_with_age_in_3_min_intervals_in_the_15_min_Open_Field_test_/760161", "title"=>"Activity with age in 3 min intervals in the 15 min Open Field test.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-07-30 11:12:39"}
  • {"files"=>["https://ndownloader.figshare.com/files/1137515"], "description"=>"<p><b>A.</b><b> </b> Distance, percentage of time spent in the opened and closed arms, and percentage of entries done in the opened and closed arms in a 5 min test on the elevated plus maze. <b>B.</b> Immobility time recorded in a 6 min tail suspension test. <b>C.</b> Immobility time recorded in a 6 min forced swimming test. Data are means ± SEM, number of animals are indicated in the corresponding bar of the histogram. The brackets indicate data given only as indication; these data were not included in the statistics due to the small size of the group considered.</p>", "links"=>[], "tags"=>["genetics", "Animal genetics", "Model organisms", "Animal models", "mouse", "neuroscience", "Behavioral neuroscience", "Motor systems", "Clinical research design", "Animal models of disease", "Mental health", "psychiatry", "Mood disorders", "Neuropsychiatric disorders", "neurology", "Parkinson disease", "depression-like", "behaviors", "bac", "tg", "ntg", "mice"], "article_id"=>760163, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Zoë Bichler", "Han Chi Lim", "Li Zeng", "Eng King Tan"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0070249.g003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Anxiety_and_depression_like_behaviors_in_BAC_LRRK2_R1441G_Tg_and_NTg_mice_with_age_/760163", "title"=>"Anxiety and depression-like behaviors in BAC <i>LRRK2<sup>R1441G</sup></i> Tg and NTg mice with age.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-07-30 11:12:39"}
  • {"files"=>["https://ndownloader.figshare.com/files/1137516"], "description"=>"<p>A. Olfaction tests at 6 and 14 months old. <b>a-d.</b> Wooden block test average time sniffing the familiar block in trial 1 to 6 (a), block preferences in trial 7 (b), and time sniffing the blocks within trials at 6 months (c) and 14 months (d). <b>e–f.</b> Latency to find and begin to eat the hidden food within trials in 8 NTg and 6 Tg mice aged 6 months old, and (e) average of latencies to find and eat the hidden food in the same mice (f). “D1” to “D5” represent “Day 1” to “Day 5” and “Surf” or “Surface” means “Surface test” occurring on the 6<sup>th</sup> day of testing. <b>B.</b> Time licking and biting the injured paw in the early and late phases of the 30 min formalin test in mice at 6, 9 and 21 months old. Data are means ± SEM, number of animals are indicated in the corresponding bar of the histogram.</p>", "links"=>[], "tags"=>["genetics", "Animal genetics", "Model organisms", "Animal models", "mouse", "neuroscience", "Behavioral neuroscience", "Motor systems", "Clinical research design", "Animal models of disease", "Mental health", "psychiatry", "Mood disorders", "Neuropsychiatric disorders", "neurology", "Parkinson disease", "functions", "tg", "ntg", "mice"], "article_id"=>760164, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Zoë Bichler", "Han Chi Lim", "Li Zeng", "Eng King Tan"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0070249.g004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Sensory_functions_of_LRRK2_R1441G_Tg_and_NTg_mice_with_age_/760164", "title"=>"Sensory functions of <i>LRRK2<sup>R1441G</sup></i> Tg and NTg mice with age.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-07-30 11:12:39"}
  • {"files"=>["https://ndownloader.figshare.com/files/1137517"], "description"=>"<p><b>A.</b> Latency to step through the white compartment with trials in the passive avoidance test. 5 NTg and 6 Tg aged 21 months old were tested up to 10 consecutive times the first day and 24 h after the last trial. <b>B–C.</b> Water content in the stool collected in one hour and dry stool weight after evaporation of the water content of Tg and NTg mice aged from 2 to 21 months old. Data are means ± SEM, number of animals are indicated in the corresponding bar of the histogram, *p<0.05, **p<0.01, ***p<0.001 with Welch’s t test for unequal variances.</p>", "links"=>[], "tags"=>["genetics", "Animal genetics", "Model organisms", "Animal models", "mouse", "neuroscience", "Behavioral neuroscience", "Motor systems", "Clinical research design", "Animal models of disease", "Mental health", "psychiatry", "Mood disorders", "Neuropsychiatric disorders", "neurology", "Parkinson disease", "abilities", "passive", "avoidance", "gastrointestinal", "dysfunction", "bac", "tg", "ntg"], "article_id"=>760165, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Zoë Bichler", "Han Chi Lim", "Li Zeng", "Eng King Tan"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0070249.g005"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Cognition_abilities_in_the_passive_avoidance_test_and_gastrointestinal_dysfunction_in_BAC_LRRK2_R1441G_Tg_and_NTg_mice_/760165", "title"=>"Cognition abilities in the passive avoidance test and gastrointestinal dysfunction in BAC <i>LRRK2<sup>R1441G</sup></i> Tg and NTg mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-07-30 11:12:39"}
  • {"files"=>["https://ndownloader.figshare.com/files/1137520"], "description"=>"<div><p>Background</p><p>Non-motor symptoms are increasingly recognized as important features of Parkinson’s disease (PD). LRRK2 mutations are common causes of familial and sporadic PD. Non-motor features have not been yet comprehensively evaluated in <i>LRRK2</i> transgenic mouse models.</p><p>Objective</p><p>Using a transgenic mouse model overexpressing the R1441G mutation of the human <i>LRRK2</i> gene, we have investigated the longitudinal correlation between motor and non-motor symptoms and determined if specific non-motor phenotypes precede motor symptoms.</p><p>Methodology</p><p>We investigated the onset of motor and non-motor phenotypes on the <i>LRRK2<sup>R1441G</sup></i> BAC transgenic mice and their littermate controls from 4 to 21 month-old using a battery of behavioral tests. The transgenic mutant mice displayed mild hypokinesia in the open field from 16 months old, with gastrointestinal dysfunctions beginning at 6 months old. Non-motor features such as depression and anxiety-like behaviors, sensorial functions (pain sensitivity and olfaction), and learning and memory abilities in the passive avoidance test were similar in the transgenic animals compared to littermate controls.</p><p>Conclusions</p><p><i>LRRK2<sup>R1441G</sup></i> BAC transgenic mice displayed gastrointestinal dysfunction at an early stage but did not have abnormalities in fine behaviors, olfaction, pain sensitivity, mood disorders and learning and memory compared to non-transgenic littermate controls. The observations on olfaction and gastrointestinal dysfunction in this model validate findings in human carriers. These mice did recapitulate mild Parkinsonian motor features at late stages but compensatory mechanisms modulating the progression of PD in these models should be further evaluated.</p></div>", "links"=>[], "tags"=>["genetics", "Animal genetics", "Model organisms", "Animal models", "mouse", "neuroscience", "Behavioral neuroscience", "Motor systems", "Clinical research design", "Animal models of disease", "Mental health", "psychiatry", "Mood disorders", "Neuropsychiatric disorders", "neurology", "Parkinson disease", "lrrk2", "transgenic"], "article_id"=>760168, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Zoë Bichler", "Han Chi Lim", "Li Zeng", "Eng King Tan"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0070249"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Non_Motor_and_Motor_Features_in_LRRK2_Transgenic_Mice_/760168", "title"=>"Non-Motor and Motor Features in LRRK2 Transgenic Mice", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-07-30 11:12:39"}

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Relative Metric

{"start_date"=>"2013-01-01T00:00:00Z", "end_date"=>"2013-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Biology and life sciences/Biomechanics", "average_usage"=>[262, 443, 579, 690, 795, 884, 991, 1089, 1183, 1275, 1366, 1445, 1522]}, {"subject_area"=>"/Biology and life sciences/Neuroscience", "average_usage"=>[261, 444, 554, 655, 748, 834, 923, 1004, 1089, 1170, 1244, 1315, 1380]}, {"subject_area"=>"/Biology and life sciences/Organisms", "average_usage"=>[281, 484, 611, 728, 835, 934, 1030, 1123, 1214, 1299, 1383, 1464]}, {"subject_area"=>"/Biology and life sciences/Physiology", "average_usage"=>[256, 449, 572, 676, 775, 866, 955, 1041, 1127, 1213, 1290, 1370, 1437]}, {"subject_area"=>"/Biology and life sciences/Psychology", "average_usage"=>[284, 458, 579, 688, 782, 879, 957, 1048, 1126, 1204, 1280, 1357, 1415]}, {"subject_area"=>"/Biology and life sciences/Zoology", "average_usage"=>[294, 473, 591, 693, 788, 883, 972, 1054, 1140, 1222, 1299, 1381, 1446]}, {"subject_area"=>"/Medicine and health sciences/Physiology", "average_usage"=>[258, 449, 572, 679, 775, 866, 956, 1041, 1124, 1211, 1291, 1371, 1437]}]}
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