title: Multiple autism-like behaviors in a novel transgenic mouse model.
abstract: Autism spectrum disorder (ASD) diagnoses are behaviorally based with no defined universal biomarkers, occur at a 1:110 ratio in the population, and predominantly affect males compared to females at approximately a 4:1 ratio. One approach to investigate and identify causes of ASD is to use organisms that display abnormal behavioral responses that model ASD-related impairments. This study describes a novel transgenic mouse, MALTT, which was generated using a forward genetics approach. It was determined that the transgene integrated within a non-coding region on the X chromosome. The MALTT line exhibited a complete repertoire of ASD-like behavioral deficits in all three domains required for an ASD diagnosis: reciprocal social interaction, communication, and repetitive or inflexible behaviors. Specifically, MALTT male mice showed deficits in social interaction and interest, abnormalities in pup and juvenile ultrasonic vocalization communications, and exhibited a repetitive stereotypy. Abnormalities were also observed in the domain of sensory function, a secondary phenotype prevalently associated with ASD. Mapping and expression studies suggested that the Fam46 gene family may be linked to the observed ASD-related behaviors. The MALTT line provides a unique genetic model for examining the underlying biological mechanisms involved in ASD-related behaviors.
authors.affiliation: Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA. sprather@bcm.edu
authors.forename: Shannon M
authors.initials: SM
authors.lastname: Hamilton
authors.forename: Corinne M
authors.initials: CM
authors.lastname: Spencer
authors.forename: Wilbur R
authors.initials: WR
authors.lastname: Harrison
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Yuva-Paylor
authors.forename: Deanna F
authors.initials: DF
authors.lastname: Graham
authors.forename: Ray A M
authors.initials: RA
authors.lastname: Daza
authors.forename: Robert F
authors.initials: RF
authors.lastname: Hevner
authors.forename: Paul A
authors.initials: PA
authors.lastname: Overbeek
authors.forename: Richard
authors.initials: R
authors.lastname: Paylor
mesh_terms: D000374:Aggression / Q000523:psychology*; D000704:Analysis of Variance; D000818:Animals; D001321:Autistic Disorder / Q000235:genetics / Q000523:psychology*; D004195:Disease Models, Animal; D005260:Female; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D055139:Sensory Gating; D012919:Social Behavior; D013239:Stereotyped Behavior; D014828:Vocalization, Animal