title: Altered social behavior and ultrasonic communication in the dystrophin-deficient mdx mouse model of Duchenne muscular dystrophy.
abstract: BACKGROUND
  The Duchenne and Becker muscular dystrophies (DMD, BMD) show significant comorbid diagnosis for autism, and the genomic sequences encoding the proteins responsible for these diseases, the dystrophin and associated proteins, have been proposed as new candidate risk loci for autism. Dystrophin is expressed not only in muscles but also in central inhibitory synapses in the cerebellum, hippocampus, amygdala, and cerebral cortex, where it contributes to the organization of autism-associated trans-synaptic neurexin-neuroligin complexes and to the clustering of synaptic gamma-aminobutyric acid (GABA)A receptors. While brain defects due to dystrophin loss are associated with deficits in cognitive and executive functions, communication skills and social behavior, only a subpopulation of DMD patients meet the criteria for autism, suggesting that mutations in the dystrophin gene may confer a vulnerability to autism. The loss of dystrophin in the mdx mouse model of DMD has been associated with cognitive and emotional alterations, but social behavior and communication abilities have never been studied in this model.
  
  
  METHODS
  Here, we carried out the first in-depth analysis of social behavior and ultrasonic communication in dystrophin-deficient mdx mice, using a range of socially relevant paradigms involving various degrees of executive and cognitive demands, from simple presentation of sexual olfactory stimuli to social choice situations and direct encounters with female and male mice of various genotypes.
  
  
  RESULTS
  We identified context-specific alterations in social behavior and ultrasonic vocal communication in mdx mice during direct encounters in novel environments. Social behavior disturbances depended on intruders' genotype and behavior, suggesting alterations in executive functions and adaptive behaviors, and were associated with selective alterations of the development, rate, acoustic properties, and use of the ultrasonic vocal repertoire.
  
  
  CONCLUSIONS
  This first evidence that a mutation impeding expression of brain dystrophin affects social behavior and communication sheds new light on critical cognitive, emotional, and conative factors contributing to the development of autistic-like traits in this disease model.
authors.affiliation: CNRS, Neuroscience Paris Saclay Institute, UMR 9197, Orsay, 91405 France ; Univ Paris-Sud, UMR 9197, Orsay, 91405 France ; Present address: Department of Psychobiology, Universidad Complutense de Madrid, Ciudad Universitaria, 28040 Madrid, Spain.
authors.forename: Rubén
authors.initials: R
authors.lastname: Miranda
authors.affiliation: CNRS, Neuroscience Paris Saclay Institute, UMR 9197, Orsay, 91405 France ; Univ Paris-Sud, UMR 9197, Orsay, 91405 France.
authors.forename: Flora
authors.initials: F
authors.lastname: Nagapin
authors.affiliation: CNRS, Neuroscience Paris Saclay Institute, UMR 9197, Orsay, 91405 France ; Univ Paris-Sud, UMR 9197, Orsay, 91405 France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Bozon
authors.affiliation: CNRS, Neuroscience Paris Saclay Institute, UMR 9197, Orsay, 91405 France ; Univ Paris-Sud, UMR 9197, Orsay, 91405 France.
authors.forename: Serge
authors.initials: S
authors.lastname: Laroche
authors.affiliation: CNRS, Neuroscience Paris Saclay Institute, UMR 9197, Orsay, 91405 France ; Univ Paris-Sud, UMR 9197, Orsay, 91405 France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Aubin
authors.affiliation: CNRS, Neuroscience Paris Saclay Institute, UMR 9197, Orsay, 91405 France ; Univ Paris-Sud, UMR 9197, Orsay, 91405 France.
authors.forename: Cyrille
authors.initials: C
authors.lastname: Vaillend
keywords: Autism; Dystroglycan; Dystrophin; Dystrophinopathies; Executive functions; Mdx mice; Neuroligin; Social behavior; Ultrasonic vocalizations