This article is a US Government work and, as such, is in the public domain in the United States of America.
Designing mouse behavioral tasks relevant to autistic-like behaviors†
Article first published online: 21 JAN 2005
Published 2004 Wiley-Liss, Inc.
Mental Retardation and Developmental Disabilities Research Reviews
Special Issue: An Update on Autism Research
Volume 10, Issue 4, pages 248–258, November 2004
How to Cite
Crawley, J. N. (2004), Designing mouse behavioral tasks relevant to autistic-like behaviors. Ment. Retard. Dev. Disabil. Res. Rev., 10: 248–258. doi: 10.1002/mrdd.20039
- Issue published online: 21 JAN 2005
- Article first published online: 21 JAN 2005
- Manuscript Accepted: 22 NOV 2004
- Manuscript Received: 17 NOV 2004
- University of North Carolina STAART Center. Grant Number: MH66418
- University of North Carolina Mental Retardation and Developmental Disorders Research Center. Grant Number: NICHD P30
- National Institute of Mental Health Intramural Research Program
- social interaction;
- ultrasonic vocalizaitons;
- olfactory communication;
- reversal learning;
- social approach;
The importance of genetic factors in autism has prompted the development of mutant mouse models to advance our understanding of biological mechanisms underlying autistic behaviors. Mouse models of human neuropsychiatric diseases are designed to optimize (1) face validity, i.e., resemblance to the human symptoms; (2) construct validity, i.e., similarity to the underlying causes of the disease; and (3) predictive validity, i.e., expected responses to treatments that are effective in the human disease. There is a growing need for mouse behavioral tasks with all three types of validity for modeling the symptoms of autism. We are in the process of designing a set of tasks with face validity for the defining features of autism: deficits in appropriate reciprocal social interactions, deficits in verbal social communication, and high levels of ritualistic repetitive behaviors. Social approach is tested in an automated three-chambered apparatus that offers the subject a choice between a familiar environment, a novel environment, and a novel environment containing a stranger mouse. Preference for social novelty is tested in the same apparatus, with a choice between the start chamber, the chamber containing a familiar mouse, and the chamber containing a stranger mouse. Social communication is evaluated by measuring the ultrasonic distress vocalizations emitted by infant mouse pups and the parental response of retrieving the pup to the nest. Resistance to change in ritualistic repetitive behaviors is modeled by forcing a change in habit, including reversal of the spatial location of a reinforcer in a T-maze task and in the Morris water maze. Mouse behavioral tasks that may model additional features of autism are discussed, including tasks relevant to anxiety, seizures, sleep disturbances, and sensory hypersensitivity. Applications of these tests include (1) behavioral phenotyping of transgenic and knockout mice with mutations in genes relevant to autism, (2) characterization of mutant mice derived from random chemical mutagenesis, (3) DNA microarray analyses of genes in inbred strains of mice that differ in social interaction, social communication and resistance to change in habit, and (4) evaluation of proposed therapeutics for the treatment of autism. Published 2004 Wiley-Liss, Inc. MRDD Research Reviews 2004;10:248–258.