Adeno-Associated Virus-Mediated Rescue of the Cognitive Defects in a Mouse Model for Angelman Syndrome
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{"title"=>"Adeno-associated virus-mediated rescue of the cognitive defects in a mouse model for Angelman syndrome", "type"=>"journal", "authors"=>[{"first_name"=>"Jennifer L.", "last_name"=>"Daily", "scopus_author_id"=>"12809147900"}, {"first_name"=>"Kevin", "last_name"=>"Nash", "scopus_author_id"=>"36961714800"}, {"first_name"=>"Umesh", "last_name"=>"Jinwal", "scopus_author_id"=>"6507238466"}, {"first_name"=>"Todd", "last_name"=>"Golde", "scopus_author_id"=>"7005214095"}, {"first_name"=>"Justin", "last_name"=>"Rogers", "scopus_author_id"=>"31767684400"}, {"first_name"=>"Melinda M.", "last_name"=>"Peters", "scopus_author_id"=>"13007496100"}, {"first_name"=>"Rebecca D.", "last_name"=>"Burdine", "scopus_author_id"=>"6602681393"}, {"first_name"=>"Chad", "last_name"=>"Dickey", "scopus_author_id"=>"7006161183"}, {"first_name"=>"Jessica L.", "last_name"=>"Banko", "scopus_author_id"=>"8906478100"}, {"first_name"=>"Edwin J.", "last_name"=>"Weeber", "scopus_author_id"=>"6603832326"}], "year"=>2011, "source"=>"PLoS ONE", "identifiers"=>{"pui"=>"363060400", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "issn"=>"19326203", "doi"=>"10.1371/journal.pone.0027221", "scopus"=>"2-s2.0-83055173238", "pmid"=>"22174738", "sgr"=>"83055173238"}, "id"=>"45a44d8a-1250-3ac2-ba14-baf1af98fc5c", "abstract"=>"Angelman syndrome (AS), a genetic disorder occurring in approximately one in every 15,000 births, is characterized by severe mental retardation, seizures, difficulty speaking and ataxia. The gene responsible for AS was discovered to be UBE3A and encodes for E6-AP, an ubiquitin ligase. A unique feature of this gene is that it undergoes maternal imprinting in a neuron-specific manner. In the majority of AS cases, there is a mutation or deletion in the maternally inherited UBE3A gene, although other cases are the result of uniparental disomy or mismethylation of the maternal gene. While most human disorders characterized by severe mental retardation involve abnormalities in brain structure, no gross anatomical changes are associated with AS. However, we have determined that abnormal calcium/calmodulin-dependent protein kinase II (CaMKII) regulation is seen in the maternal UBE3A deletion AS mouse model and is responsible for the major phenotypes. Specifically, there is an increased αCaMKII phosphorylation at the autophosphorylation sites Thr(286) and Thr(305/306), resulting in an overall decrease in CaMKII activity. CaMKII is not produced until after birth, indicating that the deficits associated with AS are not the result of developmental abnormalities. The present studies are focused on exploring the potential to rescue the learning and memory deficits in the adult AS mouse model through the use of an adeno-associated virus (AAV) vector to increase neuronal UBE3A expression. These studies show that increasing the levels of E6-AP in the brain using an exogenous vector can improve the cognitive deficits associated with AS. Specifically, the associative learning deficit was ameliorated in the treated AS mice compared to the control AS mice, indicating that therapeutic intervention may be possible in older AS patients.", "link"=>"http://www.mendeley.com/research/adenoassociated-virusmediated-rescue-cognitive-defects-mouse-model-angelman-syndrome", "reader_count"=>52, "reader_count_by_academic_status"=>{"Unspecified"=>2, "Professor > Associate Professor"=>2, "Researcher"=>12, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>17, "Student > Postgraduate"=>2, "Other"=>2, "Student > Master"=>10, "Student > Bachelor"=>3, "Lecturer > Senior Lecturer"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>2, "Professor > Associate Professor"=>2, "Researcher"=>12, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>17, "Student > Postgraduate"=>2, "Other"=>2, "Student > Master"=>10, "Student > Bachelor"=>3, "Lecturer > Senior Lecturer"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>4, "Biochemistry, Genetics and Molecular Biology"=>4, "Agricultural and Biological Sciences"=>21, "Medicine and Dentistry"=>9, "Neuroscience"=>7, "Sports and Recreations"=>1, "Business, Management and Accounting"=>1, "Psychology"=>3, "Social Sciences"=>2}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>9}, "Neuroscience"=>{"Neuroscience"=>7}, "Social Sciences"=>{"Social Sciences"=>2}, "Sports and Recreations"=>{"Sports and Recreations"=>1}, "Psychology"=>{"Psychology"=>3}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>21}, "Business, Management and Accounting"=>{"Business, Management and Accounting"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>4}, "Unspecified"=>{"Unspecified"=>4}}, "reader_count_by_country"=>{"Netherlands"=>2}, "group_count"=>5}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/704083"], "description"=>"<p>(A) Representative coronal slices through the hippocampus from each group stained for E6-AP. (B) Quantitative analysis of the IHC revealed a significant increase in E6-AP expression in the WT and AS-TR2-UBE3A mice compared to the AS TR2-GFP group, while there was no significant change between the WT and AS TR2-UBE3A mice. Results shown represent the mean with standard error.</p>", "links"=>[], "tags"=>["levels", "restored", "wildtype", "tr2-ube3a", "treated"], "article_id"=>374417, "categories"=>["Neuroscience", "Genetics", "Developmental Biology"], "users"=>["Jennifer L. Daily", "Kevin Nash", "Umesh Jinwal", "Todd Golde", "Justin Rogers", "Melinda M. Peters", "Rebecca D. Burdine", "Chad Dickey", "Jessica L. Banko", "Edwin J. Weeber"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0027221.g001", "stats"=>{"downloads"=>2, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_E6_AP_protein_levels_were_restored_to_wildtype_levels_in_the_TR2_UBE3A_treated_AS_mice_/374417", "title"=>"E6-AP protein levels were restored to wildtype levels in the TR2-UBE3A treated AS mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 10:54:37"}
  • {"files"=>["https://ndownloader.figshare.com/files/704254"], "description"=>"<p>(A) There was no change in latency to fall of the rotorod in either AS group. (B) Total distance travelled during the open field test revealed no significant difference between any of the treatment groups. (C) Time spent in the open arms of the elevated plus maze was used to determine general anxiety. (D) Time spent immobile in the elevated plus maze was not significantly different in any of the groups. Results shown represent the mean with standard error.</p>", "links"=>[], "tags"=>["changes"], "article_id"=>374610, "categories"=>["Neuroscience", "Genetics", "Developmental Biology"], "users"=>["Jennifer L. Daily", "Kevin Nash", "Umesh Jinwal", "Todd Golde", "Justin Rogers", "Melinda M. Peters", "Rebecca D. Burdine", "Chad Dickey", "Jessica L. Banko", "Edwin J. Weeber"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0027221.g003", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_There_were_no_changes_in_motor_coordination_activity_levels_or_anxiety_/374610", "title"=>"There were no changes in motor coordination, activity levels, or anxiety.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 10:55:40"}
  • {"files"=>["https://ndownloader.figshare.com/files/704481"], "description"=>"<p>(A) Escape latency to reach the platform during 5 days of training in Morris water maze. The only significant differences seen were an increase in latency for the AS TR2-GFP mice on day 3 and a decrease in latency for wildtype mice on day 4 compared to the other two groups (2-way ANOVA Bonferroni: Interaction [F(8,100) = 1.01, <i>P>0.05</i>]; Treatment [F(2,100) = 5.30, <i>P<0.05</i>]; Time [F(4,100) = 53.49, <i>P<0.0001</i>]; Matching [F(25,100) = 5.37, <i>P<0.0001</i>]). The target platform is indicated by the black circles. (B) Quantification of the number of platform crossings in the target (T), opposite (O), right (R), and left (L) quadrants during the probe trial of the Morris water maze 24 hours after training indicate no significant differences among any of the groups in comparing target platform crossings to opposite platform crossings (ANOVA Tukey WT: [F(3,35) = 9.546, <i>P<0.0005</i>]; AS TR2-GFP: [F(3,35) = 3.186, <i>P<0.01</i>]; AS TR2-UBE3A: [F(3,39) = 2.814, <i>P<0.05</i>]). All three groups learned the platform location based on a spatial bias as indicated by the time spent in the target quadrants (<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0027221#pone-0027221-g005\" target=\"_blank\">Fig. 5D</a> 24 h ANOVA Tukey [F(2,26) = 1.027, <i>P>0.05</i>]) (C) A probe test 72 hours after training indicate that the WT and AS TR2-UBE3A groups had significantly more target platform crossings compared to the number of opposite platform crossings (ANOVA Tukey WT: [F(3,35) = 6.086, <i>P<0.005</i>]; AS TR2-GFP: [F(3,35) = 0.5650, <i>P>0.05</i>]; AS TR2-UBE3A: [F(3,39) = 2.679, <i>P<0.05</i>]), but this improvement was not spatially biased as seen by the time spent in the target quadrant (<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0027221#pone-0027221-g005\" target=\"_blank\">Fig. 5D</a> 72 h ANOVA Tukey [F(2,25) = 5.067, <i>P<0.02</i>]). Results shown represent the mean with standard error.</p>", "links"=>[], "tags"=>["tr2-ube3a", "mice", "had", "improvements", "morris"], "article_id"=>374823, "categories"=>["Neuroscience", "Genetics", "Developmental Biology"], "users"=>["Jennifer L. Daily", "Kevin Nash", "Umesh Jinwal", "Todd Golde", "Justin Rogers", "Melinda M. Peters", "Rebecca D. Burdine", "Chad Dickey", "Jessica L. Banko", "Edwin J. Weeber"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0027221.g005", "stats"=>{"downloads"=>0, "page_views"=>19, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_AS_TR2_UBE3A_mice_had_significant_improvements_in_the_Morris_water_maze_/374823", "title"=>"AS TR2-UBE3A mice had significant improvements in the Morris water maze.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 10:56:55"}
  • {"files"=>["https://ndownloader.figshare.com/files/704394"], "description"=>"<p>(A) There were no differences during the training phase of fear conditioning, indicating that all groups of mice were capable of freezing to the same extent. (B) AS TR2-GFP mice show significant deficits in contextual fear conditioning when assessed 24 h after training. AS TR2-UBE3A mice, however, froze at the same rate as the wildtype mice. Results shown represent the mean with standard error.</p>", "links"=>[], "tags"=>["mice", "receiving", "tr2-ube3a", "had", "improvements", "associative"], "article_id"=>374741, "categories"=>["Neuroscience", "Genetics", "Developmental Biology"], "users"=>["Jennifer L. Daily", "Kevin Nash", "Umesh Jinwal", "Todd Golde", "Justin Rogers", "Melinda M. Peters", "Rebecca D. Burdine", "Chad Dickey", "Jessica L. Banko", "Edwin J. Weeber"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0027221.g004", "stats"=>{"downloads"=>1, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_AS_mice_receiving_TR2_UBE3A_had_significant_improvements_in_associative_learning_/374741", "title"=>"AS mice receiving TR2-UBE3A had significant improvements in associative learning.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 10:56:24"}
  • {"files"=>["https://ndownloader.figshare.com/files/704166"], "description"=>"<p>(A) AS TR2-GFP mice have significant deficits in hippocampal synaptic plasticity. LTP was induced following 20 min of baseline recordings. (B) Immediately following TBS, acute hippocampal slices taken from AS TR2-GFP mice had significant deficits in the average PTP (average of first 5 min recordings of fEPSPs slopes). To compare late phase LTP, the last 5 min recordings of fEPSPs slopes were averaged, and there was no significant difference between any of the groups. (C) There were no significant differences between any of the groups in either PPF or (D) PTP, indicating that short term synaptic plasticity mechanisms are unaffected. Results shown represent the mean with standard error.</p>", "links"=>[], "tags"=>["e6-ap", "improvements"], "article_id"=>374521, "categories"=>["Neuroscience", "Genetics", "Developmental Biology"], "users"=>["Jennifer L. Daily", "Kevin Nash", "Umesh Jinwal", "Todd Golde", "Justin Rogers", "Melinda M. Peters", "Rebecca D. Burdine", "Chad Dickey", "Jessica L. Banko", "Edwin J. Weeber"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0027221.g002", "stats"=>{"downloads"=>1, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Increasing_E6_AP_in_the_AS_mouse_results_in_improvements_in_early_phase_LTP_/374521", "title"=>"Increasing E6-AP in the AS mouse results in improvements in early phase LTP.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 10:55:13"}

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Relative Metric

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