1. Borthwell RM, Hunsaker MR, Willemsen R, Berman RF. {{Spatiotemporal processing deficits in female CGG KI mice modeling the fragile X premutation}}. {Behav Brain Res};2012 (Jul 15);233(1):29-34.
The fragile X premutation is a tandem CGG trinucleotide repeat expansion in the fragile X mental retardation 1 (FMR1) gene between 55 and 200 repeats in length. A CGG knock-in (CGG KI) mouse has been developed that models the neuropathology and cognitive deficits reported in fragile X premutation carriers. It has been suggested that carriers of the premutation demonstrate a spatiotemporal hypergranularity, or reduced resolution of spatial and temporal processing. A temporal ordering of spatial locations task was used to evaluate the ability of CGG KI mice to process temporal and spatial information with either high or low levels of spatial interference. The results indicate that CGG KI mice showed difficulty performing a spatial novelty detection task when there were high levels of spatial interference, but were able to perform the novelty detection task when there was low spatial interference. These data suggest that CGG KI mice show reduced spatial and temporal resolution that are modulated by the dosage of the Fmr1 gene mutation, such that when behavioral tasks require mice to overcome high levels of either spatial or temporal interference, the CGG KI mice perform increasingly poorly as the CGG repeat length increases.
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2. Lacaria M, Spencer C, Gu W, Paylor R, Lupski JR. {{Enriched rearing improves behavioral responses of an animal model for CNV-based autistic-like traits}}. {Hum Mol Genet};2012 (Jul 15);21(14):3083-3096.
Potocki-Lupski syndrome (PTLS; MIM #610883), characterized by neurobehavioral abnormalities, intellectual disability and congenital anomalies, is caused by a 3.7-Mb duplication in 17p11.2. Neurobehavioral studies determined that approximately 70-90% of PTLS subjects tested positive for autism or autism spectrum disorder (ASD). We previously chromosomally engineered a mouse model for PTLS (Dp(11)17/+) with a duplication of a 2-Mb genomic interval syntenic to the PTLS region and identified consistent behavioral abnormalities in this mouse model. We now report extensive phenotyping with behavioral assays established to evaluate core and associated autistic-like traits, including tests for social abnormalities, ultrasonic vocalizations, perseverative and stereotypic behaviors, anxiety, learning and memory deficits and motor defects. Alterations were identified in both core and associated ASD-like traits. Rearing this animal model in an enriched environment mitigated some, and even rescued selected, neurobehavioral abnormalities, suggesting a role for gene-environment interactions in the determination of copy number variation-mediated autism severity.
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3. Pearson BL, Bettis JK, Meyza KZ, Yamamoto LY, Blanchard DC, Blanchard RJ. {{Absence of social conditioned place preference in BTBR T+tf/J mice: Relevance for social motivation testing in rodent models of autism}}. {Behav Brain Res};2012 (Jul 15);233(1):99-104.
A major goal of translation research in autism is to characterize the physiological and psychological processes underlying behavioral abnormalities. Since autism reflects impairments in social motivation, we modified the mouse three-chamber social approach apparatus for use as a social conditioned place preference arena. We paired one of two unique contexts with social interactions in juvenile mice for five or ten conditioning sessions in BTBR T+tf/J mice and a control strain with normal approach behaviors (C57BL/6J) since the BTBR T+tf/J inbred mouse strain displays a variety of behavioral alterations analogous to symptoms of autism spectrum disorders. While C57BL/6J mice formed a conditioned place preference to the context associated with social interactions, particularly those receiving ten days of conditioning, BTBR T+tf/J mice did not. Neither absence of social proximity nor avoidance due to high rates of autogrooming appeared to underlie the impaired positive incentive value of the unconditioned social stimulus in the BTBR T+tf/J strain. These data contribute to a growing body of evidence suggesting that the BTBR T+tf/J strain shows impairments in all diagnostic domains of autism including social motivation. Additionally, social conditioning testing might provide an important social motivation measure in other rodent models of neuropsychiatric disorders characterized by social abnormalities.
