Literature DB >> 31961493

Generation of a Novel Rat Model of Angelman Syndrome with a Complete Ube3a Gene Deletion.

Andie Dodge1, Melinda M Peters1, Hayden E Greene1, Clifton Dietrick1, Robert Botelho1, Diana Chung1, Jonathan Willman1, Austin W Nenninger1, Stephanie Ciarlone1,2, Siddharth G Kamath1, Pavel Houdek3, Alena Sumová3, Anne E Anderson4, Scott V Dindot5, Elizabeth L Berg6, Henriette O'Geen7, David J Segal7, Jill L Silverman6, Edwin J Weeber1,2, Kevin R Nash1.   

Abstract

Angelman syndrome (AS) is a rare genetic disorder characterized by severe intellectual disability, seizures, lack of speech, and ataxia. The gene responsible for AS was identified as Ube3a and it encodes for E6AP, an E3 ubiquitin ligase. Currently, there is very little known about E6AP's mechanism of action in vivo or how the lack of this protein in neurons may contribute to the AS phenotype. Elucidating the mechanistic action of E6AP would enhance our understanding of AS and drive current research into new avenues that could lead to novel therapeutic approaches that target E6AP's various functions. To facilitate the study of AS, we have generated a novel rat model in which we deleted the rat Ube3a gene using CRISPR. The AS rat phenotypically mirrors human AS with loss of Ube3a expression in the brain and deficits in motor coordination as well as learning and memory. This model offers a new avenue for the study of AS. Autism Res 2020, 13: 397-409.
© 2020 International Society for Autism Research,Wiley Periodicals, Inc. LAY SUMMARY: Angelman syndrome (AS) is a rare genetic disorder characterized by severe intellectual disability, seizures, difficulty speaking, and ataxia. The gene responsible for AS was identified as UBE3A, yet very little is known about its function in vivo or how the lack of this protein in neurons may contribute to the AS phenotype. To facilitate the study of AS, we have generated a novel rat model in which we deleted the rat Ube3a gene using CRISPR. The AS rat mirrors human AS with loss of Ube3a expression in the brain and deficits in motor coordination as well as learning and memory. This model offers a new avenue for the study of AS. © 2020 International Society for Autism Research, Wiley Periodicals, Inc.

Entities:  

Keywords:  Angelman syndrome; E6AP; Ube3a; cognitive deficits; rat model

Year:  2020        PMID: 31961493      PMCID: PMC7787396          DOI: 10.1002/aur.2267

Source DB:  PubMed          Journal:  Autism Res        ISSN: 1939-3806            Impact factor:   5.216


  39 in total

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2.  International validation of a neurobehavioral screening battery: the IPCS/WHO collaborative study.

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Journal:  Toxicol Lett       Date:  1992-12       Impact factor: 4.372

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Authors:  Mu Yang; Jill L Silverman; Jacqueline N Crawley
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Authors:  Matthew C Judson; Alain C Burette; Courtney L Thaxton; Alaine L Pribisko; Mark D Shen; Ashley M Rumple; Wilmer A Del Cid; Beatriz Paniagua; Martin Styner; Richard J Weinberg; Benjamin D Philpot
Journal:  J Neurosci       Date:  2017-06-29       Impact factor: 6.167

5.  Ube3a-ATS is an atypical RNA polymerase II transcript that represses the paternal expression of Ube3a.

Authors:  Linyan Meng; Richard E Person; Arthur L Beaudet
Journal:  Hum Mol Genet       Date:  2012-04-05       Impact factor: 6.150

6.  Hypersociability in the Angelman syndrome mouse model.

Authors:  David C Stoppel; Matthew P Anderson
Journal:  Exp Neurol       Date:  2017-04-11       Impact factor: 5.330

7.  Validation of open:closed arm entries in an elevated plus-maze as a measure of anxiety in the rat.

Authors:  S Pellow; P Chopin; S E File; M Briley
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8.  Mutation of the Angelman ubiquitin ligase in mice causes increased cytoplasmic p53 and deficits of contextual learning and long-term potentiation.

Authors:  Y H Jiang; D Armstrong; U Albrecht; C M Atkins; J L Noebels; G Eichele; J D Sweatt; A L Beaudet
Journal:  Neuron       Date:  1998-10       Impact factor: 17.173

Review 9.  Organisation of the circadian system in melatonin-proficient C3H and melatonin-deficient C57BL mice: a comparative investigation.

Authors:  Jörg H Stehle; Charlotte von Gall; Horst-Werner Korf
Journal:  Cell Tissue Res       Date:  2002-05-25       Impact factor: 5.249

10.  Use of the light/dark test for anxiety in adult and adolescent male rats.

Authors:  Andrew E Arrant; Nicole L Schramm-Sapyta; Cynthia M Kuhn
Journal:  Behav Brain Res       Date:  2013-05-27       Impact factor: 3.332

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Authors:  N A Copping; J L Silverman
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4.  Functional rescue in an Angelman syndrome model following treatment with lentivector transduced hematopoietic stem cells.

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5.  Insulin-like growth factor-2 does not improve behavioral deficits in mouse and rat models of Angelman Syndrome.

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Journal:  Mol Autism       Date:  2021-09-15       Impact factor: 7.509

6.  Circadian Rhythms and Sleep Are Dependent Upon Expression Levels of Key Ubiquitin Ligase Ube3a.

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Review 7.  Recent Advances in the Production of Genome-Edited Rats.

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Review 9.  Emerging Gene and Small Molecule Therapies for the Neurodevelopmental Disorder Angelman Syndrome.

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10.  Gait as a quantitative translational outcome measure in Angelman syndrome.

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Journal:  Autism Res       Date:  2022-03-10       Impact factor: 4.633

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