Assessing the requirements of prenatal UBE3A expression for rescue of behavioral phenotypes in a mouse model for Angelman syndrome

Molecular Autism
Monica SonzogniYpe Elgersma


Angelman syndrome (AS) is a rare neurodevelopmental disorder caused by the loss of functional ubiquitin protein ligase E3A (UBE3A). In neurons, UBE3A expression is tightly regulated by a mechanism of imprinting which suppresses the expression of the paternal UBE3A allele. Promising treatment strategies for AS are directed at activating paternal UBE3A gene expression. However, for such strategies to be successful, it is important to know when such a treatment should start, and how much UBE3A expression is needed for normal embryonic brain development. Using a conditional mouse model of AS, we further delineated the critical period for UBE3A expression during early brain development. Ube3a gene expression was induced around the second week of gestation and mouse phenotypes were assessed using a behavioral test battery. To investigate the requirements of embryonic UBE3A expression, we made use of mice in which the paternal Ube3a allele was deleted. We observed a full behavioral rescue of the AS mouse model phenotypes when Ube3a gene reactivation was induced around the start of the last week of mouse embryonic development. We found that full silencing of the paternal Ube3a allele was not completed till the first week after birth bu...Continue Reading


Dec 1, 1987·American Journal of Medical Genetics·R Ellen MagenisS LaFranchi
Jan 1, 1997·Nature Genetics·Tatsuya KishinoJoseph Wagstaff
Sep 1, 1997·Nature Genetics·C RougeulleM Lalande
Sep 7, 2000·The Journal of Comparative Neurology·T D PalmerF H Gage
Apr 3, 2001·Nature Reviews. Neuroscience·A Alvarez-BuyllaA D Tramontin
Mar 16, 2002·Neurobiology of Disease·Kiyonori MiuraJoseph Wagstaff
Nov 2, 2005·Nature Reviews. Neuroscience·Takao K Hensch
Feb 14, 2006·American Journal of Medical Genetics. Part a·Charles A WilliamsJoseph Wagstaff
Apr 17, 2008·Human Molecular Genetics·Detlef H HeckLawrence T Reiter
Apr 28, 2010·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·Sayuri SuzukiHideyuki Okano
Aug 11, 2010·Neurobiology of Disease·Shalaka A Mulherkar, Nihar Ranjan Jana
Dec 23, 2011·Nature·Hsien-Sung HuangBenjamin D Philpot
Apr 3, 2012·Annual Review of Neuroscience·Christiaan N Levelt, Mark Hübener
Jan 9, 2013·Behavioural Brain Research·Hsien-Sung HuangSheryl S Moy
Apr 26, 2013·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Alan D WorkmanBarbara L Finlay
Nov 21, 2013·The Journal of Comparative Neurology·Matthew C JudsonBenjamin D Philpot
Apr 14, 2015·The Journal of Clinical Investigation·Sara Silva-SantosYpe Elgersma
Oct 21, 2015·The Journal of Clinical Investigation·Caroline F BruinsmaYpe Elgersma
Nov 25, 2015·Life Sciences·Sulagna Dutta, Pallav Sengupta
May 19, 2017·Epigenetics & Chromatin·Paul R HillmanScott V Dindot
Aug 18, 2017·Scientific Reports·Heather A BornAnne E Anderson
May 31, 2019·Molecular Autism·Monica SonzogniYpe Elgersma
Sep 7, 2019·Autism Research : Official Journal of the International Society for Autism Research·Mark J Zylka

Related Concepts

Embryonic Development
Gene Deletion
Gene Expression
Laboratory mice
Angelman Syndrome
UBE3A protein, human

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Angelman Syndrome

Angelman syndrome is a neurogenetic imprinting disorder caused by loss of the maternally inherited UBE3A gene and is characterized by generalized epilepsy, limited expressive speech, sleep dysfunction, and movement disorders. Here is the latest research.