Autism is a neurodevelopmental disorder that affects approximately 1% of the U.S. population. The causes of autism spectrum disorders are under intense investigation, with strong evidence for genetic substrates. Lifetime costs of caring for autistic individuals are high, both in terms of a) quality of life for the affected individuals and their families;b) financial expenses to the families, educational systems, and health care agencies. Discovery of multiple gene mutations, copy number variants, and epigenetic factors in people with autism has spurred the development of mouse models with homologous mutations. Genetic manipulations in mice offer an optimized experimental strategy to understand the consequences of candidate gene mutations. Effective treatments for the core symptoms of autism are currently limited to early behavioral interventions. Discovery of effective pharmacological treatments requires a greater understanding of the risk genes, biological mechanisms, and environmental factors that contribute to the etiology of autism. Animal models with robust phenotypes relevant to the diagnostic symptoms of autism offer an optimized experimental strategy to test the efficacy and safety of proposed treatments. Our Laboratory of Behavioral Neuroscience (LBN) is an international leader in behavioral assays for transgenic and knockout mice with mutations in genes expressed in brain pathways involved in neuropsychiatric disorders. We collaborate with a large number of molecular genetics laboratories that contribute mutant lines of mice with mutations in risk genes for autism to our research program. For FY12 we concentrated on winding down the activities of the laboratory in preparation for the departure of its PI to a new position at another academic institution.

Project Start
Project End
Budget Start
Budget End
Support Year
27
Fiscal Year
2012
Total Cost
$974,415
Indirect Cost
Name
U.S. National Institute of Mental Health
Department
Type
DUNS #
City
State
Country
Zip Code
Silverman, Jill L; Babineau, Brooke A; Oliver, Chicora F et al. (2013) Influence of stimulant-induced hyperactivity on social approach in the BTBR mouse model of autism. Neuropharmacology 68:210-22
Brielmaier, Jennifer; Matteson, Paul G; Silverman, Jill L et al. (2012) Autism-relevant social abnormalities and cognitive deficits in engrailed-2 knockout mice. PLoS One 7:e40914
Ey, E; Yang, M; Katz, A M et al. (2012) Absence of deficits in social behaviors and ultrasonic vocalizations in later generations of mice lacking neuroligin4. Genes Brain Behav 11:928-41
Tsai, Peter T; Hull, Court; Chu, YunXiang et al. (2012) Autistic-like behaviour and cerebellar dysfunction in Purkinje cell Tsc1 mutant mice. Nature 488:647-51
Yang, Mu; Bozdagi, Ozlem; Scattoni, Maria Luisa et al. (2012) Reduced excitatory neurotransmission and mild autism-relevant phenotypes in adolescent Shank3 null mutant mice. J Neurosci 32:6525-41
Silverman, Jill L; Smith, Daniel G; Rizzo, Stacey J Sukoff et al. (2012) Negative allosteric modulation of the mGluR5 receptor reduces repetitive behaviors and rescues social deficits in mouse models of autism. Sci Transl Med 4:131ra51
Yang, Mu; Abrams, Danielle N; Zhang, James Y et al. (2012) Low sociability in BTBR T+tf/J mice is independent of partner strain. Physiol Behav 107:649-62
Veenstra-VanderWeele, Jeremy; Muller, Christopher L; Iwamoto, Hideki et al. (2012) Autism gene variant causes hyperserotonemia, serotonin receptor hypersensitivity, social impairment and repetitive behavior. Proc Natl Acad Sci U S A 109:5469-74
Babineau, Brooke A; Yang, Mu; Crawley, Jacqueline N (2012) Mainstreaming mice. Neuropsychopharmacology 37:300-1
Papaleo, F; Yang, F; Garcia, S et al. (2012) Dysbindin-1 modulates prefrontal cortical activity and schizophrenia-like behaviors via dopamine/D2 pathways. Mol Psychiatry 17:85-98

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