A behavioral test battery for mouse models of Angelman syndrome: a powerful tool for testing drugs and novel Ube3a mutants

Molecular Autism
Monica SonzogniYpe Elgersma

Abstract

Angelman syndrome (AS) is a neurodevelopmental disorder caused by mutations affecting UBE3A function. AS is characterized by intellectual disability, impaired motor coordination, epilepsy, and behavioral abnormalities including autism spectrum disorder features. The development of treatments for AS heavily relies on the ability to test the efficacy of drugs in mouse models that show reliable, and preferably clinically relevant, phenotypes. We previously described a number of behavioral paradigms that assess phenotypes in the domains of motor performance, repetitive behavior, anxiety, and seizure susceptibility. Here, we set out to evaluate the robustness of these phenotypes when tested in a standardized test battery. We then used this behavioral test battery to assess the efficacy of minocycline and levodopa, which were recently tested in clinical trials of AS. We combined data of eight independent experiments involving 111 Ube3a mice and 120 wild-type littermate control mice. Using a meta-analysis, we determined the statistical power of the subtests and the effect of putative confounding factors, such as the effect of sex and of animal weight on rotarod performance. We further assessed the robustness of these phenotypes by com...Continue Reading

References

Jan 1, 1997·Nature Genetics·Tatsuya KishinoJoseph Wagstaff
Sep 6, 2001·Journal of Clinical Neuroscience : Official Journal of the Neurosurgical Society of Australasia·M Harbord
Mar 16, 2002·Neurobiology of Disease·Kiyonori MiuraJoseph Wagstaff
Apr 30, 2002·International Journal of Antimicrobial Agents·D Andes, W A Craig
Jul 21, 2005·The European Journal of Neuroscience·Abigail M BrownRoger J Colbran
Jan 6, 2006·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Chanhung Z LeeWilliam L Young
Feb 14, 2006·American Journal of Medical Genetics. Part a·Charles A WilliamsJoseph Wagstaff
Mar 24, 2006·Pharmacotherapy·Hazem F ElewaSusan C Fagan
Mar 14, 2009·Physiology & Behavior·Yann S Mineur, Wim E Crusio
Dec 25, 2009·American Journal of Medical Genetics. Part a·L AbaiedH Chaabouni
Apr 20, 2010·Italian Journal of Pediatrics·Agata FiumaraGiovanni Sorge
Feb 9, 2012·Journal of Visualized Experiments : JoVE·Adem CanTodd D Gould
Nov 2, 2012·Disease Models & Mechanisms·David M KatzLaura A Mamounas
Jan 9, 2013·Behavioural Brain Research·Hsien-Sung HuangSheryl S Moy
Feb 28, 2013·British Journal of Pharmacology·N Garrido-MesaJ Gálvez
Jul 23, 2013·PLoS Biology·Konstantinos K TsilidisJohn P A Ioannidis
Jan 17, 2014·Journal of Visualized Experiments : JoVE·Mariana Angoa-PérezDonald M Kuhn
Feb 15, 2014·Journal of Neuroscience Methods·Paulin Jirkof
Jun 17, 2014·Journal of Neuroscience Methods·Sonal Kedia, Sumantra Chattarji
Apr 14, 2015·The European Journal of Neuroscience·Whitney R HethornEdwin J Weeber
May 14, 2016·Cellular and Molecular Life Sciences : CMLS·Jiandong SunXiaoning Bi
Nov 20, 2016·American Journal of Medical Genetics. Part C, Seminars in Medical Genetics·Wen-Hann Tan, Lynne M Bird
Aug 18, 2017·Scientific Reports·Heather A BornAnne E Anderson
Sep 26, 2017·American Journal of Medical Genetics. Part a·Wen-Hann TanPaul A Rufo

Citations

Sep 11, 2019·The Journal of Clinical Investigation·Bin GuBenjamin D Philpot
Sep 7, 2019·Autism Research : Official Journal of the International Society for Autism Research·Mark J Zylka
Dec 24, 2019·Journal of Neuroscience Research·Xin Yang
Aug 21, 2020·Learning & Memory·Maria N Schultz, Jacqueline N Crawley
May 31, 2019·Molecular Autism·Monica SonzogniYpe Elgersma
Oct 28, 2020·Autism Research : Official Journal of the International Society for Autism Research·Emmanuel CruzCristina M Alberini
Nov 6, 2020·Brain and Behavior·Peter A PerrinoRoslyn Holly Fitch
Aug 29, 2020·Neuroscience and Biobehavioral Reviews·Sehrish JavedWei-Hsiang Huang
Jan 5, 2021·Current Opinion in Psychiatry·Helen S Heussler
Feb 6, 2021·Developmental Medicine and Child Neurology·Ype Elgersma, Monica Sonzogni
Jan 6, 2021·Journal of Neurodevelopmental Disorders·Jessica A Jiménez, Mark J Zylka

Related Concepts

Ube3a protein, mouse
Behavior Rating Scale
Metazoa
Behavior, Animal
Levopa
Mice, Mutant Strains
Minocycline, (4R-(4 alpha,4a beta,5a beta,12a beta))-Isomer
Angelman Syndrome
Ubiquitin-protein ligase
Clinical Trials

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