Mouse behavioral tasks relevant to autism: phenotypes of 10 inbred strains.
Three defining clinical symptoms of autism are aberrant reciprocal social interactions, deficits in social communication, and repetitive behaviors, including motor stereotypies and insistence on sameness. We developed a set of behavioral tasks designed to model components of these core symptoms in mice. Male mice from 10 inbred strains were characterized in assays for sociability, preference for social novelty, and reversal of the spatial location of the reinforcer in T-maze and Morris water maze tasks. Six strains, C57BL/6J, C57L/J, DBA/2J, FVB/NJ, C3H/HeJ, and AKR/J, showed significant levels of sociability, while A/J, BALB/cByJ, BTBR T(+)tf/J, and 129S1/SvImJ mice did not. C57BL/6J, C57L/J, DBA/2J, FVB/NJ, BALB/cByJ, and BTBR T(+)tf/J showed significant preference for social novelty, while C3H/HeJ, AKR/J, A/J, and 129S1/SvImJ did not. Normal scores on relevant control measures confirmed general health and physical abilities in all strains, ruling out artifactual explanations for social deficits. Elevated plus maze scores confirmed high anxiety-like behaviors in A/J, BALB/cByJ, and 129S1/SvImJ, which could underlie components of their low social approach. Strains that showed high levels of performance on acquisition of a T-maze task were also able to reach criterion for reversal learning. On the Morris water maze task, DBA/2J, AKR/J, BTBR T(+)tf/J, and 129S1/SvImJ failed to show significant quadrant preference during the reversal probe trial. These results highlight a dissociation between social task performance and reversal learning. BTBR T(+)tf/J is a particularly interesting strain, displaying both low social approach and resistance to change in routine on the water maze, consistent with an autism-like phenotype. Our multitask strategy for modeling symptoms of autism will be useful for investigating targeted and random gene mutations, QTLs, and microarray analyses.
Moy
Sheryl S
SS
North Carolina STAART Center for Autism Research, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA. ssmoy@med.unc.edu
Nadler
Jessica J
JJ
Young
Nancy B
NB
Perez
Antonio
A
Holloway
L Paige
LP
Barbaro
Ryan P
RP
Barbaro
Justin R
JR
Wilson
Lindsay M
LM
Threadgill
David W
DW
Lauder
Jean M
JM
Magnuson
Terry R
TR
Crawley
Jacqueline N
JN
D000818:Animals; D001321:Autistic Disorder; D004195:Disease Models, Animal; D005106:Exploratory Behavior; D005824:Genetics, Behavioral; D008297:Male; D018782:Maze Learning; D051379:Mice; D008806:Mice, Inbred AKR; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008811:Mice, Inbred DBA; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000502:physiology*; D010641:Phenotype; D012193:Reversal Learning; D012919:Social Behavior; D013045:Species Specificity