Translational Mouse Models of Autism: Advancing Toward Pharmacological Therapeutics.
Animal models provide preclinical tools to investigate the causal role of genetic mutations and environmental factors in the etiology of autism spectrum disorder (ASD). Knockout and humanized knock-in mice, and more recently knockout rats, have been generated for many of the de novo single gene mutations and copy number variants (CNVs) detected in ASD and comorbid neurodevelopmental disorders. Mouse models incorporating genetic and environmental manipulations have been employed for preclinical testing of hypothesis-driven pharmacological targets, to begin to develop treatments for the diagnostic and associated symptoms of autism. In this review, we summarize rodent behavioral assays relevant to the core features of autism, preclinical and clinical evaluations of pharmacological interventions, and strategies to improve the translational value of rodent models of autism.
MIND Institute, Department of Psychiatry and Behavioral Sciences, University of California Davis School of Medicine, Room 1001A Research 2 Building 96, 4625 2nd Avenue, Sacramento, CA 95817, USA.
Tatiana M
TM
Kazdoba
MIND Institute, Department of Psychiatry and Behavioral Sciences, University of California Davis School of Medicine, Room 1001A Research 2 Building 96, 4625 2nd Avenue, Sacramento, CA 95817, USA.
Prescott T
PT
Leach
MIND Institute, Department of Psychiatry and Behavioral Sciences, University of California Davis School of Medicine, Room 1001A Research 2 Building 96, 4625 2nd Avenue, Sacramento, CA 95817, USA.
Mu
M
Yang
MIND Institute, Department of Psychiatry and Behavioral Sciences, University of California Davis School of Medicine, Room 1001A Research 2 Building 96, 4625 2nd Avenue, Sacramento, CA 95817, USA.
Jill L
JL
Silverman
MIND Institute, Department of Psychiatry and Behavioral Sciences, University of California Davis School of Medicine, Room 1001A Research 2 Building 96, 4625 2nd Avenue, Sacramento, CA 95817, USA.
Marjorie
M
Solomon
MIND Institute, Department of Psychiatry and Behavioral Sciences, University of California Davis School of Medicine, Room 1001A Research 2 Building 96, 4625 2nd Avenue, Sacramento, CA 95817, USA. crawley@ucdavis.edu.
Jacqueline N
JN
Crawley
D000818:Animals; D001321:Autistic Disorder / Q000188:drug therapy* / Q000235:genetics*; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D012919:Social Behavior; D057170:Translational Research, Biomedical
Autism; Clinical trials; Cognition; Construct validity; Face validity; Genes; Mice; Mouse; Mutant models; Pharmacological treatment; Preclinical; Predictive validity; Rats; Repetitive behavior; Sociability; Social behavior; Translational; Ultrasonic vocalization