Kif14 Mutation Causes Severe Brain Malformation and Hypomyelination
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{"title"=>"Kif14 Mutation Causes Severe Brain Malformation and Hypomyelination", "type"=>"journal", "authors"=>[{"first_name"=>"Kohei", "last_name"=>"Fujikura", "scopus_author_id"=>"56989026300"}, {"first_name"=>"Tomiyoshi", "last_name"=>"Setsu", "scopus_author_id"=>"6603229881"}, {"first_name"=>"Kenji", "last_name"=>"Tanigaki", "scopus_author_id"=>"7005740895"}, {"first_name"=>"Takaya", "last_name"=>"Abe", "scopus_author_id"=>"12765267500"}, {"first_name"=>"Hiroshi", "last_name"=>"Kiyonari", "scopus_author_id"=>"6701823323"}, {"first_name"=>"Toshio", "last_name"=>"Terashima", "scopus_author_id"=>"55921311100"}, {"first_name"=>"Toshiaki", "last_name"=>"Sakisaka", "scopus_author_id"=>"6602539520"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"scopus"=>"2-s2.0-84871855606", "sgr"=>"84871855606", "issn"=>"19326203", "doi"=>"10.1371/journal.pone.0053490", "pmid"=>"23308235", "pui"=>"368048121"}, "id"=>"dff16108-432f-3670-b47b-a582675e18c8", "abstract"=>"We describe a novel spontaneous mouse mutant, laggard (lag), characterized by a flat head, motor impairment and growth retardation. The mutation is inherited as an autosomal recessive trait, and lag/lag mice suffer from cerebellar ataxia and die before weaning. lag/lag mice exhibit a dramatic reduction in brain size and slender optic nerves. By positional cloning, we identify a splice site mutation in Kif14. Transgenic complementation with wild-type Kif14-cDNA alleviates ataxic phenotype in lag/lag mice. To further confirm that the causative gene is Kif14, we generate Kif14 knockout mice and find that all of the phenotypes of Kif14 knockout mice are similar to those of lag/lag mice. The main morphological abnormality of lag/lag mouse is severe hypomyelination in central nervous system. The lag/lag mice express an array of myelin-related genes at significantly reduced levels. The disrupted cytoarchitecture of the cerebellar and cerebral cortices appears to result from apoptotic cell death. Thus, we conclude that Kif14 is essential for the generation and maturation of late-developing structures such as the myelin sheath, cerebellar and cerebral cortices. So far, no Kif14-deficient mice or mutation in Kif14 has ever been reported and we firstly define the biological function of Kif14 in vivo. The discovery of mammalian models, laggard, has opened up horizons for researchers to add more knowledge regarding the etiology and pathology of brain malformation.", "link"=>"http://www.mendeley.com/research/kif14-mutation-causes-severe-brain-malformation-hypomyelination", "reader_count"=>22, "reader_count_by_academic_status"=>{"Researcher"=>6, "Student > Ph. D. Student"=>7, "Student > Master"=>1, "Other"=>1, "Student > Bachelor"=>4, "Lecturer"=>1, "Professor"=>2}, "reader_count_by_user_role"=>{"Researcher"=>6, "Student > Ph. D. Student"=>7, "Student > Master"=>1, "Other"=>1, "Student > Bachelor"=>4, "Lecturer"=>1, "Professor"=>2}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>4, "Agricultural and Biological Sciences"=>11, "Medicine and Dentistry"=>1, "Neuroscience"=>5, "Sports and Recreations"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Neuroscience"=>{"Neuroscience"=>5}, "Sports and Recreations"=>{"Sports and Recreations"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>11}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>4}}, "group_count"=>1}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/515554"], "description"=>"<p>(A) Littermate wild type cerebellar cortex sagittal sections and the adjoining sections at P14 were counterstained with hematoxylin (Aa and Ab) and immunostained with the anti-calbindin antibody (Ac and Ad). (Ab) and (Ad) are enlarged images of the boxed areas in (Aa) and (Ac), respectively. DC, deep cerebellar nuclei; IC, inferior colliculus; IGrL, internal granule cell layer; ML, molecular layer; OGrL, outer granule cell layer; PCL, Purkinje cell layer; SC, superior colliculus. Bars in (Aa) and (Ac), 1 mm. Bars in (Ab) and (Ad), 100 µm. (B) <i>lag</i> mutant cerebellar cortex sagittal sections and the adjoining sections at P14 were counterstained with hematoxylin (Ba and Bb) and immunostained with the anti-calbindin antibody (Bc and Bd). (Bb) and (Bd) are enlarged images of the boxed areas in (Ba) and (Bc), respectively. DC, deep cerebellar nuclei; IC, inferior colliculus; IGrL, internal granule cell layer; ML, molecular layer; OGrL, outer granule cell layer; PCL, Purkinje cell layer; SC, superior colliculus. Bars in (Ba) and (Bc), 1 mm. Bars in (Bb) and (Bd), 100 µm. (C) Laminar structure of the cerebellum. Littermate wild type and <i>lag</i> mutant cerebellar cortex sagittal sections and the adjoining sections at P14 were counterstained with hematoxylin and immunostained with the anti-calbindin antibody. Bars, 100 µm. (D) Littermate wild type (Da) and <i>lag</i> mutant (Db) cerebellar cortex sagittal sections at P12 were immunostained with the anti-cleaved caspase-3 antibody. Littermate wild type (Dc) and <i>lag</i> mutant (Dd) cerebellar cortex sagittal sections at P12 were subjected to TUNEL (terminal deoxynucleotide transferase mediated dUTP nick end labeling) analysis. The insets are enlarged images of the boxed areas. Bars, 100µm.</p>", "links"=>[], "tags"=>["cytoarchitecture", "cerebellar", "cortex"], "article_id"=>186048, "categories"=>["Neuroscience", "Genetics"], "users"=>["Kohei Fujikura", "Tomiyoshi Setsu", "Kenji Tanigaki", "Takaya Abe", "Hiroshi Kiyonari", "Toshio Terashima", "Toshiaki Sakisaka"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0053490.g008", "stats"=>{"downloads"=>2, "page_views"=>38, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Disrupted_cytoarchitecture_of_the_cerebellar_cortex_of_lag_lag_mice_/186048", "title"=>"Disrupted cytoarchitecture of the cerebellar cortex of <i>lag/lag</i> mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-01-04 01:40:48"}
  • {"files"=>["https://ndownloader.figshare.com/files/514821"], "description"=>"<p>(A) The <i>lag</i> mutant phenotype. The littermate normal control mouse and the <i>lag</i> mutant mouse faced each other. Upper panel: general appearance. Lower panel: enlarged head image. Asterisk indicates the mutant mouse and red arrow indicates the flat head of the mutant mouse. (B) Behavior test for ataxia. Quantitative analysis of the duration the littermate normal control mice (n = 16) and the <i>lag</i> mutant mice (n = 16) stood on a narrow platform. Error bars represent SD. (C) Survival curves. Survival rate of the littermate normal control mice (open circles, n = 41) and the <i>lag</i> mutant mice (closed circles, n = 18) from postnatal day 1 (P1) to P25. (D) Whole brain images of the littermate normal control mouse and the <i>lag</i> mutant mouse at P12. Arrowheads indicate the translucent olfactory bulb and spinal cord of the <i>lag</i> mutant brain. Bar, 10 mm.</p>", "links"=>[], "tags"=>["mutation", "preferentially", "affects"], "article_id"=>185312, "categories"=>["Neuroscience", "Genetics"], "users"=>["Kohei Fujikura", "Tomiyoshi Setsu", "Kenji Tanigaki", "Takaya Abe", "Hiroshi Kiyonari", "Toshio Terashima", "Toshiaki Sakisaka"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0053490.g001", "stats"=>{"downloads"=>0, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_lag_mutation_preferentially_affects_the_brain_/185312", "title"=>"<i>lag</i> mutation preferentially affects the brain.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-01-04 01:28:32"}
  • {"files"=>["https://ndownloader.figshare.com/files/515687"], "description"=>"<p>(A) Littermate wild type (Aa) and <i>lag</i> mutant (Ab) whole brain coronal sections at P14 were counterstained with hematoxylin. (Ac) and (Ad) are enlarged from boxed areas in (Aa) and (Ab), respectively. (Ae) and (Af) are enlarged form (Ac) and (Ad), respectively. The arrows in (Af) indicate ectopic large pyramidal cells in layer 1. Bars in (Aa) and (Ab), 1 mm. Bars in (Ac) and (Ad), 200 µm. Bars in (Ae) and (Af), 100 µm. (B) Littermate wild type (Ba) and <i>lag</i> mutant (Bb) whole brain coronal sections at P14 were immunostained with the anti-Cux1. Littermate wild type (Be) and <i>lag</i> mutant (Bf) were immunostained with the anti-Foxp2 antibody. (Bc), (Bd), (Bg) and (Bh) are enlarged from boxed areas in (Ba), (Bb), (Be) and (Bf), respectively. Bars in (Ba), (Bb), (Be) and (Bf), 1 mm. Bars in (Bc), (Bd), (Bg) and (Bh), 200 µm. (C) The number of Cux1- and Foxp2-immunopositive cells in the cerebral cortex of the wild type and <i>lag</i> mutant mice. Cell counts were performed at 100 µm intervals using a counting grid. (D) Littermate wild type (Da) and <i>lag</i> mutant (Db) hippocampal sagittal sections at P14 were counterstained with hematoxylin. CA, Cornu Ammonis; S, subiculum; DG, dentate gyrus. Bars, 1 mm.</p>", "links"=>[], "tags"=>["cytoarchitecture", "neocortex"], "article_id"=>186179, "categories"=>["Neuroscience", "Genetics"], "users"=>["Kohei Fujikura", "Tomiyoshi Setsu", "Kenji Tanigaki", "Takaya Abe", "Hiroshi Kiyonari", "Toshio Terashima", "Toshiaki Sakisaka"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0053490.g009", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Disrupted_cytoarchitecture_in_the_neocortex_and_hippocampus_/186179", "title"=>"Disrupted cytoarchitecture in the neocortex and hippocampus.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-01-04 01:42:59"}
  • {"files"=>["https://ndownloader.figshare.com/files/514921"], "description"=>"<p> (A) LOD score plot of the <i>lag</i> locus on chromosome 1 for the F2 intercrosses. The microsatellite markers are shown on the lower side. (B) Fine mapping analysis of the <i>lag</i> locus. Black boxes represent DBA/2N allele homozygotes; white boxes represent C57BL/6 allele homozygotes and heterozygotes. The identification number of each mouse is listed at the top (# number). (C) Candidate genes mapped to the crucial region. <i>Kif14</i> exon-intron structure, positions of the 3′ UTR, and start site of translation are indicated according to the NCBI reference assembly build 37. (D) G/A substitution at the 3′ splice acceptor site of <i>Kif14</i> exon 5. The genomic sequence analysis of exon5 splice junction of <i>Kif14</i> gene was performed. The red asterisk denotes the mutation site for <i>lag</i>.</p>", "links"=>[], "tags"=>["cloning", "mutant"], "article_id"=>185414, "categories"=>["Neuroscience", "Genetics"], "users"=>["Kohei Fujikura", "Tomiyoshi Setsu", "Kenji Tanigaki", "Takaya Abe", "Hiroshi Kiyonari", "Toshio Terashima", "Toshiaki Sakisaka"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0053490.g002", "stats"=>{"downloads"=>2, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Positional_cloning_of_Kif14_in_the_lag_mutant_mouse_/185414", "title"=>"Positional cloning of <i>Kif14</i> in the <i>lag</i> mutant mouse.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-01-04 01:30:14"}
  • {"files"=>["https://ndownloader.figshare.com/files/515339"], "description"=>"<p>(A) Littermate wild type (Aa) and <i>lag/lag</i> mutant (Ab) whole brain sagittal sections at P14 were immunostained with the anti-MBP antibody. ac, anterior commissure; cc, corpus callosum; fi, fimbria; Hi, hippocampus; OB, olfactory bulb; Pn, pontine nuclei. Bars, 1 mm. (B) Littermate wild type (Ba) and <i>lag</i> mutant (Bb) spinal cord coronal sections at P14 were immunostained with the anti-MBP antibody. (Bc) is an enlarged image of the boxed area in (Bb). AH, anterior funiculus; df, dorsal funiculus; PH, posterior funiculus; py, pyramidal tract. Bars in (Ba) and (Bb), 1 mm. Bar in (Bc), 200 µm. (C) Protein levels of various myelin components in the brains of both the littermate wild type and the <i>lag</i> mutant mice. Myelin-related proteins from whole brain extracts from +/+, <i>lag</i>/+ and <i>lag</i>/<i>lag</i> mice were analyzed by quantitative immunoblotting with various antibodies against the indicated proteins. 18 µg of protein for Kif14 detection. 12 µg of protein for MAG, CNPase, MBP, and β-tubulin detection. Arrow indicates full-length Kif14. Asterisk indicates the non-specific band. (D) Oligodendrocyte morphology in the littermate wild type and the <i>lag</i> mutant mice. Upper panels: semi-thin sections of optic nerves were stained with toluidine blue. Star indicates enlargement of subarachnoid space. Bars, 1 mm. Lower panels: higher magnification of the optic nerves using transmission electron microscopy. OL, oligodendrocyte. Bars, 5 µm. (E) The number of oligodendrocytes in cross section of optic nerve (n = 6). Error bars represent SD.</p>", "links"=>[], "tags"=>["genetics and genomics", "neuroscience"], "article_id"=>185831, "categories"=>["Neuroscience", "Genetics"], "users"=>["Kohei Fujikura", "Tomiyoshi Setsu", "Kenji Tanigaki", "Takaya Abe", "Hiroshi Kiyonari", "Toshio Terashima", "Toshiaki Sakisaka"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0053490.g006", "stats"=>{"downloads"=>1, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Hypomyelination_in_lag_lag_mice_/185831", "title"=>"Hypomyelination in <i>lag/lag</i> mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-01-04 01:37:11"}
  • {"files"=>["https://ndownloader.figshare.com/files/278825", "https://ndownloader.figshare.com/files/278853", "https://ndownloader.figshare.com/files/278918", "https://ndownloader.figshare.com/files/278946", "https://ndownloader.figshare.com/files/278977", "https://ndownloader.figshare.com/files/279012"], "description"=>"<div><p>We describe a novel spontaneous mouse mutant, <em>laggard</em> (<em>lag</em>), characterized by a flat head, motor impairment and growth retardation. The mutation is inherited as an autosomal recessive trait, and <em>lag</em>/<em>lag</em> mice suffer from cerebellar ataxia and die before weaning. <em>lag</em>/<em>lag</em> mice exhibit a dramatic reduction in brain size and slender optic nerves. By positional cloning, we identify a splice site mutation in <em>Kif14</em>. Transgenic complementation with wild-type <em>Kif14</em>-cDNA alleviates ataxic phenotype in <em>lag/lag</em> mice. To further confirm that the causative gene is <em>Kif14</em>, we generate <em>Kif14</em> knockout mice and find that all of the phenotypes of <em>Kif14</em> knockout mice are similar to those of <em>lag/lag</em> mice. The main morphological abnormality of <em>lag/lag</em> mouse is severe hypomyelination in central nervous system. The <em>lag/lag</em> mice express an array of myelin-related genes at significantly reduced levels. The disrupted cytoarchitecture of the cerebellar and cerebral cortices appears to result from apoptotic cell death. Thus, we conclude that <em>Kif14</em> is essential for the generation and maturation of late-developing structures such as the myelin sheath, cerebellar and cerebral cortices. So far, no <em>Kif14</em>-deficient mice or mutation in <em>Kif14</em> has ever been reported and we firstly define the biological function of <em>Kif14 in vivo</em>. The discovery of mammalian models, <em>laggard</em>, has opened up horizons for researchers to add more knowledge regarding the etiology and pathology of brain malformation.</p> </div>", "links"=>[], "tags"=>["mutation", "causes", "malformation", "hypomyelination"], "article_id"=>114986, "categories"=>["Neuroscience", "Genetics"], "users"=>["Kohei Fujikura", "Tomiyoshi Setsu", "Kenji Tanigaki", "Takaya Abe", "Hiroshi Kiyonari", "Toshio Terashima", "Toshiaki Sakisaka"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0053490.s001", "https://dx.doi.org/10.1371/journal.pone.0053490.s002", "https://dx.doi.org/10.1371/journal.pone.0053490.s003", "https://dx.doi.org/10.1371/journal.pone.0053490.s004", "https://dx.doi.org/10.1371/journal.pone.0053490.s005", "https://dx.doi.org/10.1371/journal.pone.0053490.s006"], "stats"=>{"downloads"=>5, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Kif14_Mutation_Causes_Severe_Brain_Malformation_and_Hypomyelination__/114986", "title"=>"<em>Kif14</em> Mutation Causes Severe Brain Malformation and Hypomyelination", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2013-01-04 01:23:06"}
  • {"files"=>["https://ndownloader.figshare.com/files/515443"], "description"=>"<p>(A) Coronal sections of wild-type and <i>lag/lag</i> mice cerebral cortex at E17 were counterstained with the fluorescent Nissl stain Neurotrace (red) and immunostained with anti-Olig2 antibody (green). CP, cortical plate; IZ, intermediate zone; VZ/SVZ, ventricular zone/subventricular zone. Bars, 100 µm. The number of Olig2 immuno-positive cells are shown in the right panel (n = 6). Error bars represent SD. (B) Coronal sections of wild-type and <i>lag/lag</i> mice cortex at E17 were counterstained with the fluorescent Nissl stain Neurotrace (red) and immunostained with anti-PDGFRα antibody (green). Error bars represent SD. CP, cortical plate; IZ, intermediate zone; VZ/SVZ, ventricular zone/subventricular zone. Bars, 100 µm. The number of PDGFRα immuno-positive cells are shown in the right panel (n = 4). (C) Quantitative real time-PCR analysis of <i>Kif14</i>, <i>Olig2</i>, <i>Pdgfra</i> and <i>Mbp</i> in +/+, <i>lag</i>/+, <i>lag</i>/<i>lag</i> mice at E14.5 and P6. Each gene was amplified from whole brain polyA RNA. <i>β-actin</i> was used as a positive control for each real time-PCR. Error bars represent SD.</p>", "links"=>[], "tags"=>["noticeable", "opcs", "mice"], "article_id"=>185933, "categories"=>["Neuroscience", "Genetics"], "users"=>["Kohei Fujikura", "Tomiyoshi Setsu", "Kenji Tanigaki", "Takaya Abe", "Hiroshi Kiyonari", "Toshio Terashima", "Toshiaki Sakisaka"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0053490.g007", "stats"=>{"downloads"=>1, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_No_noticeable_difference_between_OPCs_of_lag_lag_mice_and_those_of_wild_type_mice_/185933", "title"=>"No noticeable difference between OPCs of lag/lag mice and those of wild type mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-01-04 01:38:53"}
  • {"files"=>["https://ndownloader.figshare.com/files/515962"], "description"=>"<p>Data of microarray analysis on RNA samples isolated from brains of P14 wild-type and mutant <i>laggard</i> mice.</p>", "links"=>[], "tags"=>["microarray", "rna", "samples", "brains", "p14", "wild-type", "mutant"], "article_id"=>186448, "categories"=>["Neuroscience", "Genetics"], "users"=>["Kohei Fujikura", "Tomiyoshi Setsu", "Kenji Tanigaki", "Takaya Abe", "Hiroshi Kiyonari", "Toshio Terashima", "Toshiaki Sakisaka"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0053490.t001", "stats"=>{"downloads"=>4, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Data_of_microarray_analysis_on_RNA_samples_isolated_from_brains_of_P14_wild_type_and_mutant_laggard_mice_/186448", "title"=>"Data of microarray analysis on RNA samples isolated from brains of P14 wild-type and mutant <i>laggard</i> mice.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-01-04 01:47:28"}
  • {"files"=>["https://ndownloader.figshare.com/files/515830"], "description"=>"<p>(A) Pregnant mice were intraperitoneally injected with BrdU 2 h before sacrifice. Littermate wild type (+/+) (Aa, Ab, Ac, Ad, Ae, Af) and mutant (<i>lag/lag</i>) (Aa’, Ab’, Ac’, Ad’, Ae’, Af’) cerebral cortex coronal sections at E12.5 and 15.5 were stained with hematoxylin, anti-BrdU antibody and TUNEL. CP, cortical plate; IZ, intermediate zone; MZ, marginal zone; VZ/SVZ, ventricular zone/subventricular zone. Bars, 100 µm. (B) The number of BrdU immuno-positive cells (n = 4). Error bars represent SD. Asterisk indicates statistical significance (<i>t</i> test; *, p<0.05). (C) The number of TUNEL immuno-positive cells in (n = 4). Cell counts were performed in the sensory-motor cortex. Error bars represent SD. Asterisks indicate statistical significance (<i>t</i> test; *, p<0.01).</p>", "links"=>[], "tags"=>["apoptosis", "proliferation", "cerebral", "cortex"], "article_id"=>186321, "categories"=>["Neuroscience", "Genetics"], "users"=>["Kohei Fujikura", "Tomiyoshi Setsu", "Kenji Tanigaki", "Takaya Abe", "Hiroshi Kiyonari", "Toshio Terashima", "Toshiaki Sakisaka"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0053490.g010", "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_increased_apoptosis_and_the_decreased_cell_proliferation_during_development_of_the_cerebral_cortex_in_lag_lag_mice_/186321", "title"=>"The increased apoptosis and the decreased cell proliferation during development of the cerebral cortex in <i>lag/lag</i> mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-01-04 01:45:21"}
  • {"files"=>["https://ndownloader.figshare.com/files/515034"], "description"=>"<p>(A) Northern blot analysis of <i>Kif14</i> mRNA. PolyA RNA from whole brains of +/+, <i>lag</i>/+, <i>lag</i>/<i>lag</i> mice was subjected to agarose gel-electrophoresis and then transferred to a nylon membrane. The membrane was hybridized with a <i>Kif14</i> cDNA probe. (B) Transcripts analysis of <i>Kif14</i> splice acceptor site mutation. Agarose gel-electrophoresis of <i>Kif14</i> PCR products from first-strand cDNA prepared from whole brains of +/+, <i>lag</i>/+, <i>lag</i>/<i>lag</i> mice. (C) Sequence analysis of the three <i>Kif14</i> transcripts identified in the <i>lag</i>/<i>lag</i> mouse. The <i>Kif14</i> transcript in the <i>lag</i>/<i>lag</i> mouse exhibited skipping of an 11-bp segment of exon 5, entire exon 5, and exons 5 and 6 as a result of a G to A substitution at the acceptor site of exon 5. (D) Western blot analysis of Kif14 protein at E14.5 and P12. Whole brain extracts (40 µg of proteins) from +/+, <i>lag</i>/+, <i>lag</i>/<i>lag</i> mice at E14.5 and P12 were subjected to SDS-PAGE, followed by immunoblotting with the anti-Kif14 rabbit polyclonal antibody. Arrow indicates full-length Kif14. Asterisk indicates the non-specific band.</p>", "links"=>[], "tags"=>["exon", "skipping", "mrna"], "article_id"=>185523, "categories"=>["Neuroscience", "Genetics"], "users"=>["Kohei Fujikura", "Tomiyoshi Setsu", "Kenji Tanigaki", "Takaya Abe", "Hiroshi Kiyonari", "Toshio Terashima", "Toshiaki Sakisaka"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0053490.g003", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Identification_of_exon_skipping_in_mRNA_from_lag_lag_mouse_/185523", "title"=>"Identification of exon skipping in mRNA from <i>lag/lag</i> mouse.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-01-04 01:32:03"}
  • {"files"=>["https://ndownloader.figshare.com/files/515225"], "description"=>"<p>(A) Schematic of the KO allele, in which exon 5 was deleted by homologous recombination in ES cells. (B) Behavior test for ataxia. Quantitative analysis of the duration the littermate wild-type mice (n = 8) and the <i>Kif14</i> KO mice (n = 8) stood on a narrow platform. Error bars represent SD. (C) The <i>Kif14</i> KO mouse phenotype. The littermate wild-type control mouse and the <i>Kif14</i> KO mouse faced each other. Red arrow indicates the flat head of the <i>Kif14</i> KO mouse. (D) Whole brain images of the littermate wild-type control mouse and the <i>Kif14</i> KO mouse at P12. Arrowheads indicate the translucent olfactory bulb and spinal cord of the <i>Kif14</i> KO brain. Bar, 5 mm. (E) Sagittal brain sections from the littermate wild-type control mouse (Ea) or <i>Kif14</i> KO mouse (Eb) at P12 were immunostained with the anti-MBP antibody. Bars, 2 mm. (F) Sagittal brain sections from the littermate wild-type control mouse (Fa) or <i>Kif14</i> KO mouse (Fb) at P12 were counterstained with hematoxylin. ac, anterior commissure; CX, cortex; DC, deep cerebellar nuclei; DG, dentate gyrus; fi, fimbria; Hi, hippocampus; Ic, inferior colliculus; OB, olfactory bulb; Pn, pontine nuclei; RMS, rostral migratory stream; Sc, superior colliculus; Spc, spinal cord. Bars, 2 mm.</p>", "links"=>[], "tags"=>["genetics and genomics", "neuroscience"], "article_id"=>185718, "categories"=>["Neuroscience", "Genetics"], "users"=>["Kohei Fujikura", "Tomiyoshi Setsu", "Kenji Tanigaki", "Takaya Abe", "Hiroshi Kiyonari", "Toshio Terashima", "Toshiaki Sakisaka"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0053490.g005", "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Gene_targeting_/185718", "title"=>"Gene targeting.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-01-04 01:35:18"}
  • {"files"=>["https://ndownloader.figshare.com/files/515121"], "description"=>"<p> (A) The transgenic rescue construct. pCAGGS-Kif14 carries a strong constitutive promoter (CAG pro, CAG promoter), mouse <i>Kif14</i> cDNA, SV40 early splice region/polyadenylation signal (pA), human cytomegalovirus immediate early enhancer (HCMVIEE), ampicillin resistance gene (Amp r) and E. coli replicate origin (ColE1 ori). (B) Transgenic mice were crossed with <i>lag</i>/+ mice to yield Tg:<i>lag</i>/+ mice. Tg:<i>lag</i>/+ mice were crossed with <i>lag</i>/<i>lag</i> mice to obtain Tg mice in a <i>lag</i>/<i>lag</i> background. (C) Expression levels of Kif14 in three lines of Tg:<i>lag</i>/<i>lag</i> mice. Whole brain extracts (20µg of proteins) from E14.5 wild-type mouse, P12 wild-type mouse, P12 <i>lag</i>/<i>lag</i> mouse, and P12 Tg:<i>lag</i>/<i>lag</i> mice lines (Tg26l:<i>lag</i>/<i>lag</i>, Tg28L:<i>lag</i>/<i>lag</i>, and Tg29L:<i>lag</i>/<i>lag</i>) were subjected to SDS-PAGE, followed by immunoblotting with the anti-Kif14 rabbit polyclonal antibody. Arrow indicates full-length Kif14. Asterisk indicates the non-specific band. (D) Behavior test for ataxia. Quantitative analysis of the duration the littermate wild type (+/+) mice (n = 16), the <i>lag</i> mutant (<i>lag/lag</i>) mice (n = 16), and the Tg:<i>lag</i>/<i>lag</i> mice (Tg#26l:<i>lag</i>/<i>lag</i>, n = 16; Tg#28L:<i>lag</i>/<i>lag</i>, n = 16; Tg#29L:<i>lag</i>/<i>lag</i>, n = 16) stood on a narrow platform. Error bars represent SD. (E) Dorsal views of P16 whole-brain from <i>Kif14</i> transgenic rescue (Tg29L:<i>lag/lag</i>) and non-transgenic littermate normal control mouse (<i>lag/</i>+) mice. Bar, 5 mm. (F) Sagittal brain sections from <i>Kif14</i> transgenic rescue (Tg29L:<i>lag/lag</i>) mouse (Fa), non-transgenic littermate normal control mouse (<i>lag/</i>+) (Fb), and <i>lag</i> mutant mouse (<i>lag/lag</i>) (Fc), at P16 were immunostained with the anti-MBP antibody. Bar, 2 mm. (G) Sagittal brain sections from <i>Kif14</i> transgenic rescue (Tg29L:<i>lag/lag</i>) mouse (Ga), non-transgenic littermate normal control mouse (<i>lag/</i>+) (Gb), and <i>lag</i> mutant mouse (<i>lag/lag</i>) (Gc), at P16 were counterstained with hematoxylin. ac, anterior commissure; CX, cortex; DC, deep cerebellar nuclei; DG, dentate gyrus; fi, fimbria; Hi, hippocampus; Ic, inferior colliculus; OB, olfactory bulb; ot, optic tract; Pn, pontine nuclei; RMS, rostral migratory stream; Sc, superior colliculus; Spc, spinal cord. Bars, 2 mm.</p>", "links"=>[], "tags"=>["genetics and genomics", "neuroscience"], "article_id"=>185610, "categories"=>["Neuroscience", "Genetics"], "users"=>["Kohei Fujikura", "Tomiyoshi Setsu", "Kenji Tanigaki", "Takaya Abe", "Hiroshi Kiyonari", "Toshio Terashima", "Toshiaki Sakisaka"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0053490.g004", "stats"=>{"downloads"=>1, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Transgene_rescue_/185610", "title"=>"<i>Transgene rescue.</i>", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-01-04 01:33:30"}

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Relative Metric

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