title: eIF4E/Fmr1 double mutant mice display cognitive impairment in addition to ASD-like behaviors.
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.
authors: Center for Neural Science, New York University, New York, NY 10003, United States.
authors: Thu N
authors: TN
authors: Huynh
authors: Center for Neural Science, New York University, New York, NY 10003, United States.
authors: Manan
authors: M
authors: Shah
authors: Center for Neural Science, New York University, New York, NY 10003, United States.
authors: So Yeon
authors: SY
authors: Koo
authors: Center for Neural Science, New York University, New York, NY 10003, United States.
authors: Kirsten S
authors: KS
authors: Faraud
authors: Center for Neural Science, New York University, New York, NY 10003, United States.
authors: Emanuela
authors: E
authors: Santini
authors: Center for Neural Science, New York University, New York, NY 10003, United States.
authors: Eric
authors: E
authors: Klann
mesh_terms: D000818:Animals; D001007:Anxiety / Q000235:genetics; D000067877:Autism Spectrum Disorder / Q000235:genetics* / Q000523:psychology*; D001522:Behavior, Animal / Q000502:physiology; D003072:Cognition Disorders / Q000235:genetics*; D003214:Conditioning, Classical / Q000502:physiology; D004195:Disease Models, Animal; D039561:Eukaryotic Initiation Factor-4E / Q000235:genetics / Q000502:physiology*; D005239:Fear / Q000502:physiology; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics / Q000502:physiology*; D006624:Hippocampus / Q000378:metabolism; D007398:Interpersonal Relations; D008297:Male; D008568:Memory / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009154:Mutation
chemical_list: D039561:Eukaryotic Initiation Factor-4E; D051860:Fragile X Messenger Ribonucleoprotein 1; C497684:Fmr1 protein, mouse; C000601282:eIF4E protein, mouse
keywords: Autism spectrum disorders; Cognition; Fragile X syndrome; Genetic models; Protein synthesis; Rodent behavior; eIF4E