Behavioral Evaluation of Angelman Syndrome Mice at Older Ages

Rebecca Dutta, Jacqueline N. Crawley

Research output: Contribution to journalArticle

Abstract

Angelman syndrome is a neurodevelopmental disorder presenting with severe deficits in motor, speech, and cognitive abilities. The primary genetic cause of Angelman syndrome is a maternally transmitted mutation in the Ube3a gene, which has been successfully modeled in Ube3a mutant mice. Phenotypes have been extensively reported in young adult Ube3a mice. Because symptoms continue throughout life in Angelman syndrome, we tested multiple behavioral phenotypes of male Ube3a mice and WT littermate controls at older adult ages. Social behaviors on both the 3-chambered social approach and male–female social interaction tests showed impairments in Ube3a at 12 months of age. Anxiety-related scores on both the elevated plus-maze and the light ↔ dark transitions assays indicated anxiety-like phenotypes in 12 month old Ube3a mice. Open field locomotion parameters were consistently lower at 12 months. Reduced general exploratory locomotion at this age prevented the interpretation of an anxiety-like phenotype, and likely impacted social tasks. Robust phenotypes in middle-aged Ube3a mice appear to result from continued motor decline. Motor deficits may provide the best outcome measures for preclinical testing of pharmacological targets, towards reductions of symptoms in adults with Angelman syndrome.

Original languageEnglish (US)
JournalNeuroscience
DOIs
StateAccepted/In press - Jan 1 2019

Fingerprint

Angelman Syndrome
Phenotype
Anxiety
Locomotion
Aptitude
Social Behavior
Interpersonal Relations
Young Adult
Outcome Assessment (Health Care)
Pharmacology
Light
Mutation
Genes

Keywords

  • 12 month old
  • Angelman
  • anxiety-related
  • exploration
  • social behavior
  • Ube3a mice

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Behavioral Evaluation of Angelman Syndrome Mice at Older Ages. / Dutta, Rebecca; Crawley, Jacqueline N.

In: Neuroscience, 01.01.2019.

Research output: Contribution to journalArticle

@article{bc36b9cca1ee4218a8da2146241c7240,
title = "Behavioral Evaluation of Angelman Syndrome Mice at Older Ages",
abstract = "Angelman syndrome is a neurodevelopmental disorder presenting with severe deficits in motor, speech, and cognitive abilities. The primary genetic cause of Angelman syndrome is a maternally transmitted mutation in the Ube3a gene, which has been successfully modeled in Ube3a mutant mice. Phenotypes have been extensively reported in young adult Ube3a mice. Because symptoms continue throughout life in Angelman syndrome, we tested multiple behavioral phenotypes of male Ube3a mice and WT littermate controls at older adult ages. Social behaviors on both the 3-chambered social approach and male–female social interaction tests showed impairments in Ube3a at 12 months of age. Anxiety-related scores on both the elevated plus-maze and the light ↔ dark transitions assays indicated anxiety-like phenotypes in 12 month old Ube3a mice. Open field locomotion parameters were consistently lower at 12 months. Reduced general exploratory locomotion at this age prevented the interpretation of an anxiety-like phenotype, and likely impacted social tasks. Robust phenotypes in middle-aged Ube3a mice appear to result from continued motor decline. Motor deficits may provide the best outcome measures for preclinical testing of pharmacological targets, towards reductions of symptoms in adults with Angelman syndrome.",
keywords = "12 month old, Angelman, anxiety-related, exploration, social behavior, Ube3a mice",
author = "Rebecca Dutta and Crawley, {Jacqueline N.}",
year = "2019",
month = "1",
day = "1",
doi = "10.1016/j.neuroscience.2019.10.027",
language = "English (US)",
journal = "Neuroscience",
issn = "0306-4522",
publisher = "Elsevier Limited",

}

TY - JOUR

T1 - Behavioral Evaluation of Angelman Syndrome Mice at Older Ages

AU - Dutta, Rebecca

AU - Crawley, Jacqueline N.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Angelman syndrome is a neurodevelopmental disorder presenting with severe deficits in motor, speech, and cognitive abilities. The primary genetic cause of Angelman syndrome is a maternally transmitted mutation in the Ube3a gene, which has been successfully modeled in Ube3a mutant mice. Phenotypes have been extensively reported in young adult Ube3a mice. Because symptoms continue throughout life in Angelman syndrome, we tested multiple behavioral phenotypes of male Ube3a mice and WT littermate controls at older adult ages. Social behaviors on both the 3-chambered social approach and male–female social interaction tests showed impairments in Ube3a at 12 months of age. Anxiety-related scores on both the elevated plus-maze and the light ↔ dark transitions assays indicated anxiety-like phenotypes in 12 month old Ube3a mice. Open field locomotion parameters were consistently lower at 12 months. Reduced general exploratory locomotion at this age prevented the interpretation of an anxiety-like phenotype, and likely impacted social tasks. Robust phenotypes in middle-aged Ube3a mice appear to result from continued motor decline. Motor deficits may provide the best outcome measures for preclinical testing of pharmacological targets, towards reductions of symptoms in adults with Angelman syndrome.

AB - Angelman syndrome is a neurodevelopmental disorder presenting with severe deficits in motor, speech, and cognitive abilities. The primary genetic cause of Angelman syndrome is a maternally transmitted mutation in the Ube3a gene, which has been successfully modeled in Ube3a mutant mice. Phenotypes have been extensively reported in young adult Ube3a mice. Because symptoms continue throughout life in Angelman syndrome, we tested multiple behavioral phenotypes of male Ube3a mice and WT littermate controls at older adult ages. Social behaviors on both the 3-chambered social approach and male–female social interaction tests showed impairments in Ube3a at 12 months of age. Anxiety-related scores on both the elevated plus-maze and the light ↔ dark transitions assays indicated anxiety-like phenotypes in 12 month old Ube3a mice. Open field locomotion parameters were consistently lower at 12 months. Reduced general exploratory locomotion at this age prevented the interpretation of an anxiety-like phenotype, and likely impacted social tasks. Robust phenotypes in middle-aged Ube3a mice appear to result from continued motor decline. Motor deficits may provide the best outcome measures for preclinical testing of pharmacological targets, towards reductions of symptoms in adults with Angelman syndrome.

KW - 12 month old

KW - Angelman

KW - anxiety-related

KW - exploration

KW - social behavior

KW - Ube3a mice

UR - http://www.scopus.com/inward/record.url?scp=85076096600&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85076096600&partnerID=8YFLogxK

U2 - 10.1016/j.neuroscience.2019.10.027

DO - 10.1016/j.neuroscience.2019.10.027

M3 - Article

C2 - 31730795

AN - SCOPUS:85076096600

JO - Neuroscience

JF - Neuroscience

SN - 0306-4522

ER -