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

Andie Dodge, Melinda M. Peters, Hayden E. Greene, Clifton Dietrick, Robert Botelho, Diana Chung, Jonathan Willman, Austin W. Nenninger, Stephanie Ciarlone, Siddharth G. Kamath, Pavel Houdek, Alena Sumová, Anne E. Anderson, Scott V. Dindot, Elizabeth L. Berg, Henriette O'Geen, David J. Segal, Jill L. Silverman, Edwin J. Weeber, Kevin R. Nash

Research output: Contribution to journalArticle

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 2019, 00: 1–12.

Original languageEnglish (US)
JournalAutism Research
DOIs
StateAccepted/In press - Jan 1 2020

Keywords

  • Angelman syndrome
  • cognitive deficits
  • E6AP
  • rat model
  • Ube3a

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology
  • Genetics(clinical)

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    Dodge, A., Peters, M. M., Greene, H. E., Dietrick, C., Botelho, R., Chung, D., Willman, J., Nenninger, A. W., Ciarlone, S., Kamath, S. G., Houdek, P., Sumová, A., Anderson, A. E., Dindot, S. V., Berg, E. L., O'Geen, H., Segal, D. J., Silverman, J. L., Weeber, E. J., & Nash, K. R. (Accepted/In press). Generation of a Novel Rat Model of Angelman Syndrome with a Complete Ube3a Gene Deletion. Autism Research. https://doi.org/10.1002/aur.2267