Mapping Pathological Phenotypes in a Mouse Model of CDKL5 Disorder
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{"title"=>"Mapping pathological phenotypes in a mouse model of CDKL5 disorder", "type"=>"journal", "authors"=>[{"first_name"=>"Elena", "last_name"=>"Amendola", "scopus_author_id"=>"25031246000"}, {"first_name"=>"Yang", "last_name"=>"Zhan", "scopus_author_id"=>"56681709000"}, {"first_name"=>"Camilla", "last_name"=>"Mattucci", "scopus_author_id"=>"55914689700"}, {"first_name"=>"Enrico", "last_name"=>"Castroflorio", "scopus_author_id"=>"56177496800"}, {"first_name"=>"Eleonora", "last_name"=>"Calcagno", "scopus_author_id"=>"24597739800"}, {"first_name"=>"Claudia", "last_name"=>"Fuchs", "scopus_author_id"=>"46761016800"}, {"first_name"=>"Giuseppina", "last_name"=>"Lonetti", "scopus_author_id"=>"15923140800"}, {"first_name"=>"Davide", "last_name"=>"Silingardi", "scopus_author_id"=>"36117339600"}, {"first_name"=>"Alexei L.", "last_name"=>"Vyssotski", "scopus_author_id"=>"6507579732"}, {"first_name"=>"Dominika", "last_name"=>"Farley", "scopus_author_id"=>"37112000100"}, {"first_name"=>"Elisabetta", "last_name"=>"Ciani", "scopus_author_id"=>"6603947685"}, {"first_name"=>"Tommaso", "last_name"=>"Pizzorusso", "scopus_author_id"=>"7004199973"}, {"first_name"=>"Maurizio", "last_name"=>"Giustetto", "scopus_author_id"=>"6602570696"}, {"first_name"=>"Cornelius T.", "last_name"=>"Gross", "scopus_author_id"=>"57192912826"}], "year"=>2014, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "scopus"=>"2-s2.0-84901371875", "pui"=>"373160699", "doi"=>"10.1371/journal.pone.0091613", "isbn"=>"1932-6203 (Electronic) 1932-6203 (Linking)", "sgr"=>"84901371875", "pmid"=>"24838000"}, "id"=>"7aabe88d-8f77-38cc-abaa-ea9937692e99", "abstract"=>"Mutations in cyclin-dependent kinase-like 5 (CDKL5) cause early-onset epileptic encephalopathy, a neurodevelopmental disorder with similarities to Rett Syndrome. Here we describe the physiological, molecular, and behavioral phenotyping of a Cdkl5 conditional knockout mouse model of CDKL5 disorder. Behavioral analysis of constitutive Cdkl5 knockout mice revealed key features of the human disorder, including limb clasping, hypoactivity, and abnormal eye tracking. Anatomical, physiological, and molecular analysis of the knockout uncovered potential pathological substrates of the disorder, including reduced dendritic arborization of cortical neurons, abnormal electroencephalograph (EEG) responses to convulsant treatment, decreased visual evoked responses (VEPs), and alterations in the Akt/rpS6 signaling pathway. Selective knockout of Cdkl5 in excitatory and inhibitory forebrain neurons allowed us to map the behavioral features of the disorder to separable cell-types. These findings identify physiological and molecular deficits in specific forebrain neuron populations as possible pathological substrates in CDKL5 disorder.", "link"=>"http://www.mendeley.com/research/mapping-pathological-phenotypes-mouse-model-cdkl5-disorder", "reader_count"=>66, "reader_count_by_academic_status"=>{"Unspecified"=>2, "Professor > Associate Professor"=>2, "Researcher"=>13, "Student > Ph. D. Student"=>15, "Student > Postgraduate"=>5, "Other"=>7, "Student > Master"=>14, "Student > Bachelor"=>7, "Professor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>2, "Professor > Associate Professor"=>2, "Researcher"=>13, "Student > Ph. D. Student"=>15, "Student > Postgraduate"=>5, "Other"=>7, "Student > Master"=>14, "Student > Bachelor"=>7, "Professor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>3, "Biochemistry, Genetics and Molecular Biology"=>6, "Agricultural and Biological Sciences"=>30, "Medicine and Dentistry"=>4, "Neuroscience"=>18, "Psychology"=>3, "Chemistry"=>1, "Computer Science"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>4}, "Neuroscience"=>{"Neuroscience"=>18}, "Chemistry"=>{"Chemistry"=>1}, "Psychology"=>{"Psychology"=>3}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>30}, "Computer Science"=>{"Computer Science"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>6}, "Unspecified"=>{"Unspecified"=>3}}, "reader_count_by_country"=>{"United States"=>1, "United Kingdom"=>2, "Germany"=>2}, "group_count"=>0}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1501330"], "description"=>"<p>(<b>A–B</b>) Representative electroencephalogram (EEG) traces recorded from surface electrodes placed over the somatosensory cortex in freely moving male wild-type (WT) and <i>Cdkl5</i> knockout (KO) mice. (<b>Left</b>) Baseline EEG before drug treatment. (<b>Right</b>) EEG taken during 2 hour post-injection period following treatment with high dose (25 mg/kg, i.p.) kainic acid. (<b>expanded trace</b>) Detail of epileptiform event showing low frequency, high amplitude activity. (<b>C</b>) Latency to the first epileptiform event did not differ between wild-type and <i>Cdkl5</i> knockout mice, but (<b>D</b>) mean duration of events was longer and (<b>E</b>) mean frequency was lower in knockouts. Average EEG power spectra of (<b>left</b>) baseline and (<b>right</b>) post-injection periods for (<b>F</b>) low dose (10 mg/kg, i.p.) and (<b>G</b>) high dose (25 mg/kg, i.p.) kainic acid treatment revealed a significant, dose-dependent increased in low frequency EEG power in wild-type, but not <i>Cdkl5</i> knockout mice (mean ± SEM; WT: N = 4, KO: N = 5).</p>", "links"=>[], "tags"=>["anatomy", "nervous system", "neuroanatomy", "cell biology", "Cell processes", "Cell cycle and cell division", "cyclins", "Cellular types", "Animal cells", "neurons", "Signal transduction", "cell signaling", "Signaling cascades", "Akt signaling cascade", "Molecular cell biology", "genetics", "Heredity", "Genetic linkage", "Sex linkage", "X-linked traits", "Rett syndrome", "Human genetics", "neuroscience", "Cellular neuroscience", "Neuronal morphology", "Developmental neuroscience", "neurogenesis", "Behavioral neuroscience", "Molecular neuroscience", "Clinical genetics", "neurology", "epilepsy", "Model organisms", "Animal models", "Mouse models", "Specimen preparation and treatment", "Mechanical treatment of specimens", "Specimen disruption", "electroporation", "seizure", "knockout"], "article_id"=>1029616, "categories"=>["Biological Sciences"], "users"=>["Elena Amendola", "Yang Zhan", "Camilla Mattucci", "Enrico Castroflorio", "Eleonora Calcagno", "Claudia Fuchs", "Giuseppina Lonetti", "Davide Silingardi", "Alexei L. Vyssotski", "Dominika Farley", "Elisabetta Ciani", "Tommaso Pizzorusso", "Maurizio Giustetto", "Cornelius T. Gross"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0091613.g003", "stats"=>{"downloads"=>4, "page_views"=>15, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Altered_seizure_response_in_Cdkl5_knockout_mice_/1029616", "title"=>"Altered seizure response in <i>Cdkl5</i> knockout mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-05-16 02:54:15"}
  • {"files"=>["https://ndownloader.figshare.com/files/1501331"], "description"=>"<p>(<b>A</b>) Representative images of reconstructed neurons from adult male wild-type (WT, top panel) and <i>Cdkl5</i> knockout (KO, bottom panel) mice. (<b>B</b>) Total dendrite length was significantly reduced in female and male <i>Cdkl5</i> knockout mice (X/X, N = 6; -/X, N = 15; -/-, N = 6; X/Y, N = 15; -/Y, N = 15). Heterozygous female knockout mice showed a bimodal distribution (K–S test, P = 1.2×10<sup>−14</sup>). (<b>C</b>) Significantly reduced cortical thickness was observed in <i>Cdkl5</i> knockout compared with WT controls in female and male mice (X/X, N = 3; -/X, N = 3; -/-, N = 3; X/Y, N = 3; -/Y, N = 3; mean ± SEM, *P<0.05, **P<0.01, ***P<0.001).</p>", "links"=>[], "tags"=>["anatomy", "nervous system", "neuroanatomy", "cell biology", "Cell processes", "Cell cycle and cell division", "cyclins", "Cellular types", "Animal cells", "neurons", "Signal transduction", "cell signaling", "Signaling cascades", "Akt signaling cascade", "Molecular cell biology", "genetics", "Heredity", "Genetic linkage", "Sex linkage", "X-linked traits", "Rett syndrome", "Human genetics", "neuroscience", "Cellular neuroscience", "Neuronal morphology", "Developmental neuroscience", "neurogenesis", "Behavioral neuroscience", "Molecular neuroscience", "Clinical genetics", "neurology", "epilepsy", "Model organisms", "Animal models", "Mouse models", "Specimen preparation and treatment", "Mechanical treatment of specimens", "Specimen disruption", "electroporation", "dendritic", "branching", "knockout"], "article_id"=>1029617, "categories"=>["Biological Sciences"], "users"=>["Elena Amendola", "Yang Zhan", "Camilla Mattucci", "Enrico Castroflorio", "Eleonora Calcagno", "Claudia Fuchs", "Giuseppina Lonetti", "Davide Silingardi", "Alexei L. Vyssotski", "Dominika Farley", "Elisabetta Ciani", "Tommaso Pizzorusso", "Maurizio Giustetto", "Cornelius T. Gross"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0091613.g004", "stats"=>{"downloads"=>2, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Abnormal_dendritic_branching_in_Cdkl5_knockout_mice_/1029617", "title"=>"Abnormal dendritic branching in <i>Cdkl5</i> knockout mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-05-16 02:54:15"}
  • {"files"=>["https://ndownloader.figshare.com/files/1501332"], "description"=>"<p>(<b>A</b>) Western blot analysis of whole brain protein extracts from adult female and male wild-type and <i>Cdkl5</i> mutant mice. Tubulin was included as a loading control. No change was seen in MeCP2 (top panel) and BDNF (lower panel) levels in mutant <i>Cdkl5</i> mice compared with wild-type controls (X/X, N = 10; -/X, N = 6; -/-, N = 10; X/Y, N = 5; -/Y, N = 6). (<b>B</b>) Western blot analysis of hyppocampal protein extracts from P19 female and male wild-type and <i>Cdkl5</i> mutant mice. Decreased pAKT was observed in Cdkl5 mutant mic4 compared with wild-type controls (X/X, N = 4; -/X, N = 6/8; -/-, N = 6; X/Y, N = 3; -/Y, N = 5. (<b>C</b>) Western blot quantification revealed a significant decrease in phospho-Akt immunoreactivity protein in mutant <i>Cdkl5</i> mice compared with wild-type controls (female: WT, N = 10, HET, N = 6, KO, N = 10; male: WT, N = 5, KO, N = 6; mean ± SEM) (mean ± SEM; *P<0.05, **P<0.01). (<b>D</b>) Representative anti-phospho-rpS6 (240/244) immunohistochemistry in the S1 cortex of adult wild-type and <i>Cdkl5</i> mutant mice. (E) Representative anti-phospho-rpS6 (235/236) immunohistochemistry in the S1 cortex of adult wild-type and <i>Cdkl5</i> mutant mice. A significant reduction of phosphorylation at serine 240/244 (<b>F</b>) and a trend for reduced phosphorylation at serine 235/236 (<b>G</b>) of rpS6 was observed in layer II–III and V of male and female mutant mice compared to wild-type controls (X/X, N = 4; -/X, N = 6; -/-, N = 3; X/Y, N = 4; -/Y, N = 4; *P<0.05, *P<0.01).</p>", "links"=>[], "tags"=>["anatomy", "nervous system", "neuroanatomy", "cell biology", "Cell processes", "Cell cycle and cell division", "cyclins", "Cellular types", "Animal cells", "neurons", "Signal transduction", "cell signaling", "Signaling cascades", "Akt signaling cascade", "Molecular cell biology", "genetics", "Heredity", "Genetic linkage", "Sex linkage", "X-linked traits", "Rett syndrome", "Human genetics", "neuroscience", "Cellular neuroscience", "Neuronal morphology", "Developmental neuroscience", "neurogenesis", "Behavioral neuroscience", "Molecular neuroscience", "Clinical genetics", "neurology", "epilepsy", "Model organisms", "Animal models", "Mouse models", "Specimen preparation and treatment", "Mechanical treatment of specimens", "Specimen disruption", "electroporation", "cellular", "signalling", "knockout"], "article_id"=>1029618, "categories"=>["Biological Sciences"], "users"=>["Elena Amendola", "Yang Zhan", "Camilla Mattucci", "Enrico Castroflorio", "Eleonora Calcagno", "Claudia Fuchs", "Giuseppina Lonetti", "Davide Silingardi", "Alexei L. Vyssotski", "Dominika Farley", "Elisabetta Ciani", "Tommaso Pizzorusso", "Maurizio Giustetto", "Cornelius T. Gross"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0091613.g005", "stats"=>{"downloads"=>5, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Defective_cellular_signalling_in_Cdkl5_knockout_mice_/1029618", "title"=>"Defective cellular signalling in <i>Cdkl5</i> knockout mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-05-16 02:54:15"}
  • {"files"=>["https://ndownloader.figshare.com/files/1501333"], "description"=>"<p>(<b>A</b>–<b>B</b>) Percentage of mice showing hind-limb clasping was significantly increased in heterozygous female and hemizygous male (<b>B</b>) <i>Emx1</i> (F/X, N = 13; F/X-<i>Emx1</i>::Cre, N = 9; F/Y, N = 12; F/Y-<i>Emx1</i>::Cre, N = 9), but not (<b>A</b>) <i>Dlx5/6</i>-conditional <i>Cdkl5</i> knockout mice (F/X, N = 7; F/X-<i>Dlx5/6</i>::Cre, N = 6; F/Y, N = 4; F/Y-<i>Dlx5/6</i>::Cre, N = 13). (<b>C–F</b>) Home cage activity was significantly decreased in (<b>E</b>) male hemizygous (F/Y, N = 6; F/Y-<i>Dlx5/6</i>::Cre, N = 13), but not (<b>C</b>) female heterozygous (F/X, N = 5; F/X-<i>Dlx5/6</i>::Cre, N = 4) <i>Dlx5/6</i>-conditional <i>Cdkl5</i> knockout mice when compared to control littermates. Normal locomotion activity was observed in (<b>D</b>) female and (<b>F</b>) male <i>Emx1</i>-conditional <i>Cdkl5</i> knockout mice when compared to control littermates (F/X, N = 12; F/X-<i>Emx1</i>::Cre, N = 6; F/Y, N = 15; F/Y-<i>Emx1</i>::Cre, N = 9). (<b>G–H</b>) Number of head tracking saccades was decreased in male, but not female <i>Emx1</i>-conditional <i>Cdkl5</i> knockout mice (F/Y, N = 7; F/Y-<i>Emx1</i>::Cre, N = 6; F/X, N = 5; F/X-<i>Emx1</i>::Cre, N = 6). No evidence for deficient head tracking was observed in <i>Dlx5/6</i>-conditional <i>Cdkl5</i> knockout mice (F/Y, N = 5; F/Y-<i>Dlx5/6</i>::Cre, N = 11; F/X, N = 5; F/X-<i>Dlx5/6</i>::Cre, N = 5; ***P<0.001, **P<0.01, *P<0.05).</p>", "links"=>[], "tags"=>["anatomy", "nervous system", "neuroanatomy", "cell biology", "Cell processes", "Cell cycle and cell division", "cyclins", "Cellular types", "Animal cells", "neurons", "Signal transduction", "cell signaling", "Signaling cascades", "Akt signaling cascade", "Molecular cell biology", "genetics", "Heredity", "Genetic linkage", "Sex linkage", "X-linked traits", "Rett syndrome", "Human genetics", "neuroscience", "Cellular neuroscience", "Neuronal morphology", "Developmental neuroscience", "neurogenesis", "Behavioral neuroscience", "Molecular neuroscience", "Clinical genetics", "neurology", "epilepsy", "Model organisms", "Animal models", "Mouse models", "Specimen preparation and treatment", "Mechanical treatment of specimens", "Specimen disruption", "electroporation", "impairments", "conditional", "knockout"], "article_id"=>1029619, "categories"=>["Biological Sciences"], "users"=>["Elena Amendola", "Yang Zhan", "Camilla Mattucci", "Enrico Castroflorio", "Eleonora Calcagno", "Claudia Fuchs", "Giuseppina Lonetti", "Davide Silingardi", "Alexei L. Vyssotski", "Dominika Farley", "Elisabetta Ciani", "Tommaso Pizzorusso", "Maurizio Giustetto", "Cornelius T. Gross"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0091613.g006", "stats"=>{"downloads"=>2, "page_views"=>19, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Behavioral_impairments_in_Cdkl5_conditional_knockout_mice_/1029619", "title"=>"Behavioral impairments in <i>Cdkl5</i> conditional knockout mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-05-16 02:54:15"}
  • {"files"=>["https://ndownloader.figshare.com/files/1501338", "https://ndownloader.figshare.com/files/1501339", "https://ndownloader.figshare.com/files/1501340", "https://ndownloader.figshare.com/files/1501341", "https://ndownloader.figshare.com/files/1501342", "https://ndownloader.figshare.com/files/1501343", "https://ndownloader.figshare.com/files/1501344", "https://ndownloader.figshare.com/files/1501345"], "description"=>"<div><p>Mutations in cyclin-dependent kinase-like 5 (<i>CDKL5</i>) cause early-onset epileptic encephalopathy, a neurodevelopmental disorder with similarities to Rett Syndrome. Here we describe the physiological, molecular, and behavioral phenotyping of a <i>Cdkl5</i> conditional knockout mouse model of CDKL5 disorder. Behavioral analysis of constitutive <i>Cdkl5</i> knockout mice revealed key features of the human disorder, including limb clasping, hypoactivity, and abnormal eye tracking. Anatomical, physiological, and molecular analysis of the knockout uncovered potential pathological substrates of the disorder, including reduced dendritic arborization of cortical neurons, abnormal electroencephalograph (EEG) responses to convulsant treatment, decreased visual evoked responses (VEPs), and alterations in the Akt/rpS6 signaling pathway. Selective knockout of <i>Cdkl5</i> in excitatory and inhibitory forebrain neurons allowed us to map the behavioral features of the disorder to separable cell-types. These findings identify physiological and molecular deficits in specific forebrain neuron populations as possible pathological substrates in CDKL5 disorder.</p></div>", "links"=>[], "tags"=>["anatomy", "nervous system", "neuroanatomy", "cell biology", "Cell processes", "Cell cycle and cell division", "cyclins", "Cellular types", "Animal cells", "neurons", "Signal transduction", "cell signaling", "Signaling cascades", "Akt signaling cascade", "Molecular cell biology", "genetics", "Heredity", "Genetic linkage", "Sex linkage", "X-linked traits", "Rett syndrome", "Human genetics", "neuroscience", "Cellular neuroscience", "Neuronal morphology", "Developmental neuroscience", "neurogenesis", "Behavioral neuroscience", "Molecular neuroscience", "Clinical genetics", "neurology", "epilepsy", "Model organisms", "Animal models", "Mouse models", "Specimen preparation and treatment", "Mechanical treatment of specimens", "Specimen disruption", "electroporation", "pathological", "phenotypes", "cdkl5"], "article_id"=>1029624, "categories"=>["Biological Sciences"], "users"=>["Elena Amendola", "Yang Zhan", "Camilla Mattucci", "Enrico Castroflorio", "Eleonora Calcagno", "Claudia Fuchs", "Giuseppina Lonetti", "Davide Silingardi", "Alexei L. Vyssotski", "Dominika Farley", "Elisabetta Ciani", "Tommaso Pizzorusso", "Maurizio Giustetto", "Cornelius T. Gross"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0091613.s001", "https://dx.doi.org/10.1371/journal.pone.0091613.s002", "https://dx.doi.org/10.1371/journal.pone.0091613.s003", "https://dx.doi.org/10.1371/journal.pone.0091613.s004", "https://dx.doi.org/10.1371/journal.pone.0091613.s005", "https://dx.doi.org/10.1371/journal.pone.0091613.s006", "https://dx.doi.org/10.1371/journal.pone.0091613.s007", "https://dx.doi.org/10.1371/journal.pone.0091613.s008"], "stats"=>{"downloads"=>23, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Mapping_Pathological_Phenotypes_in_a_Mouse_Model_of_CDKL5_Disorder_/1029624", "title"=>"Mapping Pathological Phenotypes in a Mouse Model of CDKL5 Disorder", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2014-05-16 02:54:15"}
  • {"files"=>["https://ndownloader.figshare.com/files/1501327"], "description"=>"<p>(<b>A</b>) Western blot analysis of whole brain protein extracts of wild-type (X/X), heterozygous (-/X), and homozygous (-/-) female and wild-type (X/Y) and hemizygous (-/Y) male <i>Cdkl5</i> knockout mice using polyclonal (top panel) and monoclonal (bottom panel) anti-Cdkl5 antibodies. (<b>B</b>) Immunofluorescence analysis of CA1 hippocampus brain sections from adult male wild-type (WT) and <i>Cdkl5</i> knockout (KO) mice using polyclonal anti-Cdkl5 antibody, showing staining of neuronal cell bodies and nuclear puncta (Scale bar 40 µm). (<b>C</b>) Anti-Cdkl5, SC35 and Mecp2 immunofluorescence analysis of S1 cortex brain sections from adult male wild-type (WT) mice. Arrowheads point to regions of co-localization between CDKL5 and SC35 and Mecp2 and SC32 (Scale bar 10 µm).</p>", "links"=>[], "tags"=>["anatomy", "nervous system", "neuroanatomy", "cell biology", "Cell processes", "Cell cycle and cell division", "cyclins", "Cellular types", "Animal cells", "neurons", "Signal transduction", "cell signaling", "Signaling cascades", "Akt signaling cascade", "Molecular cell biology", "genetics", "Heredity", "Genetic linkage", "Sex linkage", "X-linked traits", "Rett syndrome", "Human genetics", "neuroscience", "Cellular neuroscience", "Neuronal morphology", "Developmental neuroscience", "neurogenesis", "Behavioral neuroscience", "Molecular neuroscience", "Clinical genetics", "neurology", "epilepsy", "Model organisms", "Animal models", "Mouse models", "Specimen preparation and treatment", "Mechanical treatment of specimens", "Specimen disruption", "electroporation", "knockout"], "article_id"=>1029613, "categories"=>["Biological Sciences"], "users"=>["Elena Amendola", "Yang Zhan", "Camilla Mattucci", "Enrico Castroflorio", "Eleonora Calcagno", "Claudia Fuchs", "Giuseppina Lonetti", "Davide Silingardi", "Alexei L. Vyssotski", "Dominika Farley", "Elisabetta Ciani", "Tommaso Pizzorusso", "Maurizio Giustetto", "Cornelius T. Gross"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0091613.g001", "stats"=>{"downloads"=>2, "page_views"=>25, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Validation_of_Cdkl5_knockout_mice_/1029613", "title"=>"Validation of <i>Cdkl5</i> knockout mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-05-16 02:54:15"}
  • {"files"=>["https://ndownloader.figshare.com/files/1501329"], "description"=>"<p>(<b>A</b>–<b>B</b>) Percentage of mice showing hind-limb clasping was significantly increased in adult female and male <i>Cdkl5</i> knockout mice (X/X, N = 28; -/X, N = 38; -/-, N = 32; X/Y, N = 55; -/Y, N = 42). Home cage activity was significantly decreased in adult (<b>C</b>) female and (<b>D</b>) male <i>Cdkl5</i> knockout. (<b>E</b>) Number of eye tracking saccades was significantly decreased in adult female and male <i>Cdkl5</i> knockout mice (X/X, N = 10; -/X, N = 9; -/-, N = 10; X/Y, N = 10; -/Y, N = 11). (<b>F</b>) Amplitude of the VEP short latency wave evoked by a low spatial frequency grating (0.05 c/deg) was significantly reduced in adult female <i>Cdkl5</i> knockouts (X/X, N = 5; -/X, N = 3; -/-, N = 6; *P<0.05, **P<0.01).</p>", "links"=>[], "tags"=>["anatomy", "nervous system", "neuroanatomy", "cell biology", "Cell processes", "Cell cycle and cell division", "cyclins", "Cellular types", "Animal cells", "neurons", "Signal transduction", "cell signaling", "Signaling cascades", "Akt signaling cascade", "Molecular cell biology", "genetics", "Heredity", "Genetic linkage", "Sex linkage", "X-linked traits", "Rett syndrome", "Human genetics", "neuroscience", "Cellular neuroscience", "Neuronal morphology", "Developmental neuroscience", "neurogenesis", "Behavioral neuroscience", "Molecular neuroscience", "Clinical genetics", "neurology", "epilepsy", "Model organisms", "Animal models", "Mouse models", "Specimen preparation and treatment", "Mechanical treatment of specimens", "Specimen disruption", "electroporation", "impairments", "knockout"], "article_id"=>1029615, "categories"=>["Biological Sciences"], "users"=>["Elena Amendola", "Yang Zhan", "Camilla Mattucci", "Enrico Castroflorio", "Eleonora Calcagno", "Claudia Fuchs", "Giuseppina Lonetti", "Davide Silingardi", "Alexei L. Vyssotski", "Dominika Farley", "Elisabetta Ciani", "Tommaso Pizzorusso", "Maurizio Giustetto", "Cornelius T. Gross"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0091613.g002", "stats"=>{"downloads"=>1, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Behavioral_impairments_in_Cdkl5_knockout_mice_/1029615", "title"=>"Behavioral impairments in <i>Cdkl5</i> knockout mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-05-16 02:54:15"}

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