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Thursday, May 7, 2009: 1:30 PM
Ballroom (Chicago Hilton)
Autism is a major mental illness with a strong genetic component. As candidate genes for autism are identified, mice with targeted mutations of these genes are becoming available. Model organisms offer useful translational tools to test hypotheses about single genes, chromosomal locus deletions, copy number variants, epigenetic mechanisms, neurochemical,electrophysiological, synaptic, and neuroanatomical abnormalities, environmental toxins, diets, immune dysfunctions, and other proposed causes of autism.
The key to translational applications is robust, highly replicable functional assays. We developed mouse behavioral paradigms with conceptual analogies to the three diagnostic symptoms of autism. Abnormalities in reciprocal social interactions are assayed longitudinally across developmental ages during juvenile play, automated adult social approach, and reciprocal social interaction tasks. Communication deficits are quantitated by the emission, detection, and behavioral responses to social auditory and olfactory and cues. Motor stereotypies, repetitive behaviors, insistence on sameness, and narrow restricted interests manifest in mice as stereotyped motor behaviors, repetitive self-grooming, perseveration during the reversal phase of T-maze and Morris water maze spatial habits, and restricted exploration of complex environments. Relevant to the associated symptoms of autism, mouse models are assayed for cognitive deficits, anxiety-like traits, seizures, sleep disruption, and hyperreactivity to sensory stimuli. Comprehensive control parameters including measures of general health, reflexes, sensory and motor abilities, detect artifacts caused by physical and procedural dysfunctions.
Representative data will be presented for BTBR T+tf/J, an inbred strain of mice that displays autism-relevant traits in all three diagnostic domains, and for mice with mutations in putative candidate genes for autism. Strong phenotypes relevant to the diagnostic and associated symptoms of autism, in targeted gene mutations and inbred strains of mice, offer attractive model systems for treatment discovery. Early preclinical data will be presented on pharmacological and behavioral interventions that reverse autism-relevant behavioral phenotypes in the BTBR mouse model of autism.
The key to translational applications is robust, highly replicable functional assays. We developed mouse behavioral paradigms with conceptual analogies to the three diagnostic symptoms of autism. Abnormalities in reciprocal social interactions are assayed longitudinally across developmental ages during juvenile play, automated adult social approach, and reciprocal social interaction tasks. Communication deficits are quantitated by the emission, detection, and behavioral responses to social auditory and olfactory and cues. Motor stereotypies, repetitive behaviors, insistence on sameness, and narrow restricted interests manifest in mice as stereotyped motor behaviors, repetitive self-grooming, perseveration during the reversal phase of T-maze and Morris water maze spatial habits, and restricted exploration of complex environments. Relevant to the associated symptoms of autism, mouse models are assayed for cognitive deficits, anxiety-like traits, seizures, sleep disruption, and hyperreactivity to sensory stimuli. Comprehensive control parameters including measures of general health, reflexes, sensory and motor abilities, detect artifacts caused by physical and procedural dysfunctions.
Representative data will be presented for BTBR T+tf/J, an inbred strain of mice that displays autism-relevant traits in all three diagnostic domains, and for mice with mutations in putative candidate genes for autism. Strong phenotypes relevant to the diagnostic and associated symptoms of autism, in targeted gene mutations and inbred strains of mice, offer attractive model systems for treatment discovery. Early preclinical data will be presented on pharmacological and behavioral interventions that reverse autism-relevant behavioral phenotypes in the BTBR mouse model of autism.