Fmr1 and Nlgn3 knockout rats: Novel tools for investigating autism spectrum disorders

Shannon M. Hamilton, Jennie R. Green, Surabi Veeraragavan, Lisa Yuva, Aaron McCoy, Yumei Wu, Joe Warren, Lara Little, Diana Ji, Xiaoxia Cui, Edward Weinstein, Richard Paylor

Research output: Contribution to journalArticlepeer-review

94 Scopus citations

Abstract

Animal models are critical for gaining insights into autism spectrum disorder (ASD). Despite their apparent advantages to mice for neural studies, rats have not been widely used for disorders of the human CNS, such as ASD, for the lack of convenient genome manipulation tools. Here we describe two of the first transgenic rat models for ASD, developed using zinc-finger nuclease (ZFN) methodologies, and their initial behavioral assessment using a rapid juvenile test battery. A syndromic and nonsyndromic rat model for ASD were created as two separate knockout rat lines with heritable disruptions in the genes encoding Fragile X mental retardation protein (FMRP) and Neuroligin3 (NLGN3). FMRP, a protein with numerous proposed functions including regulation of mRNA and synaptic protein synthesis, and NLGN3, a member of the neuroligin synaptic cell-adhesion protein family, have been implicated in human ASD. Juvenile subjects from both knockout rat lines exhibited abnormalities in ASD-relevant phenotypes including juvenile play, perseverative behaviors, and sensorimotor gating. These data provide important first evidence regarding the utility of rats as genetic models for investigating ASD-relevant genes.

Original languageEnglish
Pages (from-to)103-109
Number of pages7
JournalBehavioral Neuroscience
Volume128
Issue number2
DOIs
StatePublished - Apr 1 2014

Keywords

  • Autism
  • Behavior
  • Fmr1
  • Neuroligin 3
  • Rat

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