Generation and Characterization of Conditional Heparin-Binding EGF-Like Growth Factor Knockout Mice
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{"title"=>"Generation and characterization of conditional heparin-binding EGF-like growth factor knockout mice", "type"=>"journal", "authors"=>[{"first_name"=>"Atsushi", "last_name"=>"Oyagi", "scopus_author_id"=>"23989394000"}, {"first_name"=>"Yasuhisa", "last_name"=>"Oida", "scopus_author_id"=>"13003284000"}, {"first_name"=>"Kenichi", "last_name"=>"Kakefuda", "scopus_author_id"=>"35077751400"}, {"first_name"=>"Masamitsu", "last_name"=>"Shimazawa", "scopus_author_id"=>"6602683783"}, {"first_name"=>"Norifumi", "last_name"=>"Shioda", "scopus_author_id"=>"14013674500"}, {"first_name"=>"Shigeki", "last_name"=>"Moriguchi", "scopus_author_id"=>"9635375500"}, {"first_name"=>"Kiyoyuki", "last_name"=>"Kitaichi", "scopus_author_id"=>"7004185693"}, {"first_name"=>"Daisuke", "last_name"=>"Nanba", "scopus_author_id"=>"6602308501"}, {"first_name"=>"Kazumasa", "last_name"=>"Yamaguchi", "scopus_author_id"=>"57198842097"}, {"first_name"=>"Yasuhide", "last_name"=>"Furuta", "scopus_author_id"=>"7102112718"}, {"first_name"=>"Kohji", "last_name"=>"Fukunaga", "scopus_author_id"=>"7201972807"}, {"first_name"=>"Shigeki", "last_name"=>"Higashiyama", "scopus_author_id"=>"7006490737"}, {"first_name"=>"Hideaki", "last_name"=>"Hara", "scopus_author_id"=>"56799750000"}], "year"=>2009, "source"=>"PLoS ONE", "identifiers"=>{"sgr"=>"70449338128", "pmid"=>"19829704", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "pui"=>"355609547", "issn"=>"19326203", "scopus"=>"2-s2.0-70449338128", "doi"=>"10.1371/journal.pone.0007461"}, "id"=>"f75ce9c8-e0a7-3f76-a8d7-49780a922dac", "abstract"=>"Recently, neurotrophic factors and cytokines have been shown to be associated in psychiatric disorders, such as schizophrenia, bipolar disorder, and depression. Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a member of the EGF family, serves as a neurotrophic molecular and plays a significant role in the brain. We generated mice in which HB-EGF activity is disrupted specifically in the ventral forebrain. These knockout mice showed (a) behavioral abnormalities similar to those described in psychiatric disorders, which were ameliorated by typical or atypical antipsychotics, (b) altered dopamine and serotonin levels in the brain, (c) decreases in spine density in neurons of the prefrontal cortex, (d) reductions in the protein levels of the NR1 subunit of the N-methyl-D-aspartate (NMDA) receptor and post-synaptic protein-95 (PSD-95), (e) decreases in the EGF receptor, and in the calcium/calmodulin-dependent protein kinase II (CaMK II) signal cascade. These results suggest the alterations affecting HB-EGF signaling could comprise a contributing factor in psychiatric disorder.", "link"=>"http://www.mendeley.com/research/generation-characterization-conditional-heparinbinding-egflike-growth-factor-knockout-mice", "reader_count"=>32, "reader_count_by_academic_status"=>{"Unspecified"=>2, "Professor > Associate Professor"=>6, "Researcher"=>7, "Student > Ph. D. Student"=>9, "Student > Master"=>2, "Other"=>1, "Student > Bachelor"=>2, "Lecturer"=>1, "Professor"=>2}, "reader_count_by_user_role"=>{"Unspecified"=>2, "Professor > Associate Professor"=>6, "Researcher"=>7, "Student > Ph. D. Student"=>9, "Student > Master"=>2, "Other"=>1, "Student > Bachelor"=>2, "Lecturer"=>1, "Professor"=>2}, "reader_count_by_subject_area"=>{"Unspecified"=>4, "Biochemistry, Genetics and Molecular Biology"=>2, "Materials Science"=>1, "Medicine and Dentistry"=>6, "Agricultural and Biological Sciences"=>11, "Arts and Humanities"=>1, "Neuroscience"=>2, "Pharmacology, Toxicology and Pharmaceutical Science"=>3, "Psychology"=>2}, "reader_count_by_subdiscipline"=>{"Materials Science"=>{"Materials Science"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>6}, "Neuroscience"=>{"Neuroscience"=>2}, "Psychology"=>{"Psychology"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>11}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>2}, "Unspecified"=>{"Unspecified"=>4}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>3}, "Arts and Humanities"=>{"Arts and Humanities"=>1}}, "group_count"=>1}

Scopus | Further Information

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  • {"files"=>["https://ndownloader.figshare.com/files/879446"], "description"=>"<p>(a) Gene-targeting strategy. Mouse <i>Hb-egf</i> cDNA containing the polyadenylation (pA) sequence flanked by loxP sequences was fused with the first exon of the mouse <i>Hb-egf</i> gene. The lacZ gene was inserted downstream of the <i>Hb-egf</i> cDNA. The targeting vector also contains the neomycin-resistance gene (neo), driven by the phosphoglycerate kinase (PGK) promoter and the diphtheria toxinA-fragment (DT-A) gene. Cre-mediated recombination results in the deletion of <i>Hb-egf</i> cDNA and in the expression of the lacZ gene. Exon sequences are indicated as black boxes. E, EcoR1; H, hind1; K, Kpnl; S, Sacll; V, EcoRV; X, Xhol. (b) Genotype of ventral forebrain-specific HB-EGF KO mice. Ventral forebrain-specific HB-EGF-deficient mice were confirmed by PCR as lox homozygous and Cre-recombinase positive. (c) Coronal section through the cortex region; square indicates area shown in the photomicrographs. (d) Histological analysis of cortex from controls (upper) and HB-EGF KO (lower) adult mice. LacZ staining, scale bar = 50 µm. In situ hybridization using an <i>Hb-egf</i> probe, scale bar = 100 µm. Immunohistochemical staining with anti-HB-EGF antibody, scale bar = 20 µm. Cresyl violet staining, scale bar = 500 µm. (e) Coronal section through the hippocampus; square indicates area shown in the photomicrographs (CA1, CA3, and DG). (f) LacZ staining of whole and individual hippocampal region in HB-EGF KO mice, scale bar = 500 µm. (g) Immunohistochemical analysis of individual hippocampal region from controls (upper) and HB-EGF KO (lower) adult mice, scale bar = 20 µm.</p>", "links"=>[], "tags"=>["hb-egf", "ko"], "article_id"=>549892, "categories"=>["Neuroscience", "Medicine"], "users"=>["Atsushi Oyagi", "Yasuhisa Oida", "Kenichi Kakefuda", "Masamitsu Shimazawa", "Norifumi Shioda", "Shigeki Moriguchi", "Kiyoyuki Kitaichi", "Daisuke Nanba", "Kazumasa Yamaguchi", "Yasuhide Furuta", "Kohji Fukunaga", "Shigeki Higashiyama", "Hideaki Hara"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0007461.g001", "stats"=>{"downloads"=>1, "page_views"=>18, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Generation_of_HB_EGF_KO_mice_/549892", "title"=>"Generation of HB-EGF KO mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-10-14 02:44:52"}
  • {"files"=>["https://ndownloader.figshare.com/files/880155"], "description"=>"<p>Representative images of immunoblots showing EGF receptor and β-actin (a), ErbB4 and β-actin (b), p-EGF receptor and total EGF receptor (c), p-ERK, ERK, and β-actin (d), p-Akt, Akt, and β-actin (e), and p-ErbB4 and ErbB4 (f) in the prefrontal cortex (upper). Quantitative analysis of EGF receptor (a), ErbB4 (b), p-EGF receptor (c), p-ERK (d), p-Akt (e), and p-ErbB4 (f) by densitometric scanning of immunoreactive bands, with normalization to the signals for β-actin (a and b), EGF receptor (c), ERK (d), Akt (e), or ErbB4 (f) (lower). Data for control (n = 5) and KO (n = 5) mice are expressed as a percentage of the control value. Values are means±SEM. * p<0.05 vs. control mice.</p>", "links"=>[], "tags"=>["egf", "receptor", "signals", "hb-egf", "ko"], "article_id"=>550597, "categories"=>["Neuroscience", "Medicine"], "users"=>["Atsushi Oyagi", "Yasuhisa Oida", "Kenichi Kakefuda", "Masamitsu Shimazawa", "Norifumi Shioda", "Shigeki Moriguchi", "Kiyoyuki Kitaichi", "Daisuke Nanba", "Kazumasa Yamaguchi", "Yasuhide Furuta", "Kohji Fukunaga", "Shigeki Higashiyama", "Hideaki Hara"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0007461.g006", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Expression_of_EGF_receptor_and_its_signals_in_HB_EGF_KO_and_control_mice_/550597", "title"=>"Expression of EGF receptor and its signals in HB-EGF KO and control mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-10-14 00:09:57"}
  • {"files"=>["https://ndownloader.figshare.com/files/879978"], "description"=>"<p>Representative images of immunoblotting showing total CaMKII (a), p-CaMKII (c), p-PAK1/3, and p-PAK2 (e). Quantitative analysis of total CaMKII (b), p-CaMKII (d), p-PAK1/3, and p-PAK2 (f) by densitometric scanning of immunoreactive bands. Data for control (n = 5) and KO (n = 5) mice are expressed as a percentage of the control value. Values are means±SEM. * p<0.05 vs. control mice.</p>", "links"=>[], "tags"=>["camkii", "signals", "hb-egf", "ko"], "article_id"=>550423, "categories"=>["Neuroscience", "Medicine"], "users"=>["Atsushi Oyagi", "Yasuhisa Oida", "Kenichi Kakefuda", "Masamitsu Shimazawa", "Norifumi Shioda", "Shigeki Moriguchi", "Kiyoyuki Kitaichi", "Daisuke Nanba", "Kazumasa Yamaguchi", "Yasuhide Furuta", "Kohji Fukunaga", "Shigeki Higashiyama", "Hideaki Hara"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0007461.g005", "stats"=>{"downloads"=>1, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Activation_of_CaMKII_and_its_related_signals_in_HB_EGF_KO_and_control_mice_/550423", "title"=>"Activation of CaMKII and its related signals in HB-EGF KO and control mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-10-14 00:07:03"}
  • {"files"=>["https://ndownloader.figshare.com/files/436047", "https://ndownloader.figshare.com/files/436057", "https://ndownloader.figshare.com/files/436065"], "description"=>"<div><p>Recently, neurotrophic factors and cytokines have been shown to be associated in psychiatric disorders, such as schizophrenia, bipolar disorder, and depression. Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a member of the EGF family, serves as a neurotrophic molecular and plays a significant role in the brain. We generated mice in which HB-EGF activity is disrupted specifically in the ventral forebrain. These knockout mice showed (a) behavioral abnormalities similar to those described in psychiatric disorders, which were ameliorated by typical or atypical antipsychotics, (b) altered dopamine and serotonin levels in the brain, (c) decreases in spine density in neurons of the prefrontal cortex, (d) reductions in the protein levels of the NR1 subunit of the <em>N</em>-methyl-D-aspartate (NMDA) receptor and post-synaptic protein-95 (PSD-95), (e) decreases in the EGF receptor, and in the calcium/calmodulin-dependent protein kinase II (CaMK II) signal cascade. These results suggest the alterations affecting HB-EGF signaling could comprise a contributing factor in psychiatric disorder.</p></div>", "links"=>[], "tags"=>["characterization", "conditional", "heparin-binding", "egf-like", "knockout", "mice"], "article_id"=>145988, "categories"=>["Neuroscience", "Medicine"], "users"=>["Atsushi Oyagi", "Yasuhisa Oida", "Kenichi Kakefuda", "Masamitsu Shimazawa", "Norifumi Shioda", "Shigeki Moriguchi", "Kiyoyuki Kitaichi", "Daisuke Nanba", "Kazumasa Yamaguchi", "Yasuhide Furuta", "Kohji Fukunaga", "Shigeki Higashiyama", "Hideaki Hara"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0007461.s001", "https://dx.doi.org/10.1371/journal.pone.0007461.s002", "https://dx.doi.org/10.1371/journal.pone.0007461.s003"], "stats"=>{"downloads"=>19, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Generation_and_Characterization_of_Conditional_Heparin_Binding_EGF_Like_Growth_Factor_Knockout_Mice/145988", "title"=>"Generation and Characterization of Conditional Heparin-Binding EGF-Like Growth Factor Knockout Mice", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2009-10-14 01:39:48"}
  • {"files"=>["https://ndownloader.figshare.com/files/879870"], "description"=>"<p>(a) Representative photomicrographs showing morphology of pyramidal neurons in cortical layer III of the prefrontal cortex from control (left) and KO (right) mice. Scale bar = 20 µm. (b) Representative photomicrographs of apical dendritic segments from control (left) and KO (right) mice. Scale bar = 8 µm. (c) High-magnification images of apical dendritic segments from adult control (left) and KO (right) mice. Scale bar = 2 µm. (d) Representative images of immunoblots showing NR1 and PSD-95 protein levels. (e) Quantification of the number of basal dendritic branch-points. (f) Spine density on primary apical dendrites of layer III pyramidal neurons of the prefrontal cortex from control (white bar) and KO (black bar) mice. (g) Quantification of spine length. Control (n = 700 spines) and KO (n = 592 spines) mice (n = 4 mice, 25 neurons each). (h) Cumulative distribution of spine length. Control (white circle) and KO (black circle) mice (n = 4 mice, 25 neurons each). (i, j, k, and l) Quantitative analysis of NR1, PSD-95, NR2A, and NR2B by densitometric scanning of immunoreactive bands. Control (n = 5), KO (n = 5). Data for control and KO mice are expressed as a percentage of the control value. Values are means±SEM. ** p<0.01, *** p<0.001 vs. control mice.</p>", "links"=>[], "tags"=>["changes", "prefrontal"], "article_id"=>550317, "categories"=>["Neuroscience", "Medicine"], "users"=>["Atsushi Oyagi", "Yasuhisa Oida", "Kenichi Kakefuda", "Masamitsu Shimazawa", "Norifumi Shioda", "Shigeki Moriguchi", "Kiyoyuki Kitaichi", "Daisuke Nanba", "Kazumasa Yamaguchi", "Yasuhide Furuta", "Kohji Fukunaga", "Shigeki Higashiyama", "Hideaki Hara"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0007461.g004", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Morphological_changes_in_the_prefrontal_cortex_/550317", "title"=>"Morphological changes in the prefrontal cortex.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-10-14 00:05:17"}
  • {"files"=>["https://ndownloader.figshare.com/files/879618"], "description"=>"<p>(a and b) Locomotor activity test. Mice were placed into individual cages, and their locomotion was assessed every hour for 1 day. Controls (n = 8), KO mice with treatment of vehicle (n = 7), haloperidol (n = 8), and clozapine (n = 8). (a) Locomotor activity throughout the 24-hr period, and (b) locomotor activity analyzed separately during day and night periods. (c) PPI of the acoustic startle response in control (n = 24), KO mice with treatment of vehicle (n = 24), haloperidol (n = 15), risperidone (n = 14), and clozapine (n = 12). The PPI is expressed as a percentage of the startle response to a 120 dB pulse. (d) Social interaction test in a novel environment in controls (n = 8) and KO mice with treatment of vehicle (n = 7), haloperidol (n = 9), and clozapine (n = 9). Two genetically identical mice that had been housed separately were placed in the same cage. Their social interaction was then monitored for 10 min. Values are means±SEM. (e and f) Novel-object recognition task. (e) In the training trial (5 min), two circles were placed in symmetrical left and right positions. (f) In the test trial 1 hr later (5 min), one circle (left) and one triangle (right) were placed in the same positions. The amount of time the control (n = 6) and KO (n = 6) mice spent exploring each object during training trial and test trial was recorded. * p<0.05 vs. left object. (g and h) Y-maze task. Each mouse was placed at the end of one fixed arm of the maze and allowed to move freely through the maze for 8 min. The sequence of arm entries was recorded manually. (g) Total number of arms entered during the session. (h) % of alternation was calculated as (actual alternations/maximum alternations) ×100. Control (n = 6), KO (n = 6). Values are means±SEM. * p<0.05 vs. control mice. #p<0.05, ##p<0.01 vs. vehicle-treated HB-EGF KO mice.</p>", "links"=>[], "tags"=>["hb-egf", "ko", "mice"], "article_id"=>550062, "categories"=>["Neuroscience", "Medicine"], "users"=>["Atsushi Oyagi", "Yasuhisa Oida", "Kenichi Kakefuda", "Masamitsu Shimazawa", "Norifumi Shioda", "Shigeki Moriguchi", "Kiyoyuki Kitaichi", "Daisuke Nanba", "Kazumasa Yamaguchi", "Yasuhide Furuta", "Kohji Fukunaga", "Shigeki Higashiyama", "Hideaki Hara"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0007461.g002", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Behavioral_analysis_of_HB_EGF_KO_mice_and_control_mice_/550062", "title"=>"Behavioral analysis of HB-EGF KO mice and control mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-10-14 00:01:02"}
  • {"files"=>["https://ndownloader.figshare.com/files/879740"], "description"=>"<p>Levels of monoamine neurotransmitters and their major metabolites were assayed in the (a) prefrontal cortex, (b) thalamus, (c) cerebellum, and (d) striatum of controls (n = 11) and HB-EGF KO (n = 11) mice. Values are means±SEM. * p<0.05, ** p<0.01 vs. control mice. NE: Norepinephrine, MHPG: 3-methoxy 4-hydroxy phenethyleneglycol, DA: Dopamine, DOPAC: 3,4-dihydroxyphenilacetic acid, 3-MT: 3-methoxytyramine, HVA: homovanillic acid, 5-HT: Serotonin, 5-HIAA: 5-hydroxyindol acetic acid.</p>", "links"=>[], "tags"=>["monoamine", "levels"], "article_id"=>550189, "categories"=>["Neuroscience", "Medicine"], "users"=>["Atsushi Oyagi", "Yasuhisa Oida", "Kenichi Kakefuda", "Masamitsu Shimazawa", "Norifumi Shioda", "Shigeki Moriguchi", "Kiyoyuki Kitaichi", "Daisuke Nanba", "Kazumasa Yamaguchi", "Yasuhide Furuta", "Kohji Fukunaga", "Shigeki Higashiyama", "Hideaki Hara"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0007461.g003", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Tissue_monoamine_levels_of_individual_brain_regions_/550189", "title"=>"Tissue monoamine levels of individual brain regions.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-10-14 00:03:09"}

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  • {"unique-ip"=>"8", "full-text"=>"6", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"11"}
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  • {"unique-ip"=>"4", "full-text"=>"5", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"1"}
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  • {"unique-ip"=>"3", "full-text"=>"3", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"2"}
  • {"unique-ip"=>"1", "full-text"=>"1", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"3"}
  • {"unique-ip"=>"5", "full-text"=>"4", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"3", "cited-by"=>"0", "year"=>"2019", "month"=>"4"}
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  • {"unique-ip"=>"4", "full-text"=>"2", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"8"}
  • {"unique-ip"=>"2", "full-text"=>"3", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"9"}
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Relative Metric

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