Comprehensive analysis of two Shank3 and the Cacna1c mouse models of autism spectrum disorder.

Autor: Kabitzke PA; PsychoGenics, Inc, Tarrytown, NY, USA., Brunner D; PsychoGenics, Inc, Tarrytown, NY, USA.; Department of Psychiatry, Columbia University, New York, NY, USA., He D; PsychoGenics, Inc, Tarrytown, NY, USA., Fazio PA; PsychoGenics, Inc, Tarrytown, NY, USA., Cox K; PsychoGenics, Inc, Tarrytown, NY, USA., Sutphen J; PsychoGenics, Inc, Tarrytown, NY, USA., Thiede L; PsychoGenics, Inc, Tarrytown, NY, USA., Sabath E; PsychoGenics, Inc, Tarrytown, NY, USA., Hanania T; PsychoGenics, Inc, Tarrytown, NY, USA., Alexandrov V; PsychoGenics, Inc, Tarrytown, NY, USA., Rasmusson R; Department of Physiology and Biophysics, SUNY Buffalo School of Medicine and Biomedical Sciences, Buffalo, NY, USA., Spooren W; Roche, Basel, Switzerland., Ghosh A; Roche, Basel, Switzerland., Feliciano P; Simons Foundation Autism Research Initiative, New York, NY, USA., Biemans B; Roche, Basel, Switzerland., Benedetti M; Simons Foundation Autism Research Initiative, New York, NY, USA., Clayton AL; Simons Foundation Autism Research Initiative, New York, NY, USA.
Jazyk: angličtina
Zdroj: Genes, brain, and behavior [Genes Brain Behav] 2018 Jan; Vol. 17 (1), pp. 4-22. Date of Electronic Publication: 2017 Sep 05.
DOI: 10.1111/gbb.12405
Abstrakt: To expand, analyze and extend published behavioral phenotypes relevant to autism spectrum disorder (ASD), we present a study of three ASD genetic mouse models: Feng's Shank3 tm2Gfng model, hereafter Shank3/F, Jiang's Shank3 tm1Yhj model, hereafter Shank3/J and the Cacna1c deletion model. The Shank3 models mimick gene mutations associated with Phelan-McDermid Syndrome and the Cacna1c model recapitulates the deletion underlying Timothy syndrome. This study utilizes both standard and novel behavioral tests with the same methodology used in our previously published companion report on the Cntnap2 null and 16p11.2 deletion models. We found that some but not all behaviors replicated published findings and those that did replicate, such as social behavior and overgrooming in Shank3 models, tended to be milder than reported elsewhere. The Shank3/F model, and to a much lesser extent, the Shank3/J and Cacna1c models, showed hypoactivity and a general anxiety-like behavior triggered by external stimuli which pervaded social interactions. We did not detect deficits in a cognitive procedural learning test nor did we observe perseverative behavior in these models. We did, however, find differences in exploratory patterns of Cacna1c mutant mice suggestive of a behavioral effect in a social setting. In addition, only Shank3/F showed differences in sensory-gating. Both positive and negative results from this study will be useful in identifying the most robust and replicable behavioral signatures within and across mouse models of autism. Understanding these phenotypes may shed light of which features to study when screening compounds for potential therapeutic interventions.
(© 2017 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.)
Databáze: MEDLINE
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