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Characterization of Mood and Anxiety Phenotypes in a Mouse Model of Pten Haploinsufficiency

Thursday, 2 May 2013: 09:00-13:00
Banquet Hall (Kursaal Centre)
A. Clipperton-Allen and D. Page, Department of Neuroscience, The Scripps Research Institute, Jupiter, FL
Background: Haploinsufficiency for PTEN, which encodes a negative regulator of the PI3 kinase pathway, is a risk factor for autism spectrum disorder (ASD) and macrocephaly. Using a mouse model of Pten haploinsufficiency, we have previously found that mutant mice show deficits in social approach behaviour, as well as brain overgrowth. 

Objectives: To further characterize behavioral changes in Pten haploinsufficient mice, we are testing these animals using an extensive phenotyping battery. We have a particular focus on behavioral assays that probe the serotonin pathway as a candidate neural system underlying these changes, given our previous finding that haploinsufficiency for serotonin transporter can modify phenotypes in Pten haploinsufficient mice.

Methods: Our behavioral phenotyping battery includes assays of mood and anxiety (tail suspension test and dark-light emergence), emotional learning and memory (fear conditioning), nociception and motor ability. For select assays in which Pten haploinsufficient mice display abnormalities, we are testing drugs that modulate the serotonin pathway as candidate suppressors.

Results: Results from our battery suggest that Pten haploinsufficient males display greater immobility in the tail suspension test, indicating a higher level of depression-like behaviour. We also find that Pten haploinsufficient show abnormalities in assays of dark-light emergence and fear conditioning.

Conclusions: These data indicate that haploinsufficiency for Pten results in abnormalities in mood and anxiety, as well as emotional learning and memory, with implications for understanding comorbidities in individuals with ASD. Ongoing experiments are investigating potential developmental mechanisms.

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