eIF4E/Fmr1 double mutant mice display cognitive impairment in addition to ASD-like behaviors Academic Article uri icon

Overview

MeSH Major

  • Autism Spectrum Disorder
  • Cognition Disorders
  • Disease Models, Animal
  • Eukaryotic Initiation Factor-4E
  • Fragile X Mental Retardation Protein
  • Memory

abstract

  • Autism spectrum disorder (ASD) is a group of heritable disorders with complex and unclear etiology. Classic ASD symptoms include social interaction and communication deficits as well as restricted, repetitive behaviors. In addition, ASD is often comorbid with intellectual disability. Fragile X syndrome (FXS) is the leading genetic cause of ASD, and is the most commonly inherited form of intellectual disability. Several mouse models of ASD and FXS exist, however the intellectual disability observed in ASD patients is not well modeled in mice. Using the Fmr1 knockout mouse and the eIF4E transgenic mouse, two previously characterized mouse models of fragile X syndrome and ASD, respectively, we generated the eIF4E/Fmr1 double mutant mouse. Our study shows that the eIF4E/Fmr1 double mutant mice display classic ASD behaviors, as well as cognitive dysfunction. Importantly, the learning impairments displayed by the double mutant mice spanned multiple cognitive tasks. Moreover, the eIF4E/Fmr1 double mutant mice display increased levels of basal protein synthesis. The results of our study suggest that the eIF4E/Fmr1 double mutant mouse may be a reliable model to study cognitive dysfunction in the context of ASD.

publication date

  • November 2015

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC4674395

Digital Object Identifier (DOI)

  • 10.1016/j.nbd.2015.08.016

PubMed ID

  • 26306459

Additional Document Info

start page

  • 67

end page

  • 74

volume

  • 83