Increased Levels of Anxiety-related Behaviors in a Tsc2 Dominant Negative Transgenic Mouse Model of Tuberous Sclerosis

Abstract

Tuberous sclerosis (TSC) is a single-gene disorder caused by heterozygous mutations in the TSC1 or TSC2 gene. TSC is often associated with neurological (e.g., epilepsy), cognitive (intellectual disabilities, specific neuropsychological impairments) and behavioral pathologies (e.g., autism, attention deficit hyperactivity disorder). In addition, there is a high prevalence of psychiatric problems in TSC populations, including anxiety and mood disorders. To date, little is known about the pathogenetic bases of these associated psychiatric symptoms; for instance, it is unclear whether they are rooted in TSC-associated neurobiological alterations or whether they are secondary psychological phenomena (e.g., because individuals have to cope with the burden of the disease). Here, we report elevated levels of anxiety-related behaviors and mild deficits in two hippocampal-dependent learning tasks in a Tsc2 dominant negative transgenic mouse model of TSC. These findings establish a mouse model for TSC-related anxiety phenotypes and suggest that anxiety disorders in TSC have a biological foundation.

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Acknowledgments

Tsc2-DN mice were kindly provided by Jack L. Arbiser. This work was supported by DFG grant EH223/2-1 and funds of the German Centre for Neurodegenerative Diseases (DZNE) to D.E. and NIH R01 MH084315 to A.J.S.

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Correspondence to Dan Ehninger.

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Edited by Pierre Roubertoux and Petrus de Vries.

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Ehninger, D., Silva, A.J. Increased Levels of Anxiety-related Behaviors in a Tsc2 Dominant Negative Transgenic Mouse Model of Tuberous Sclerosis. Behav Genet 41, 357–363 (2011). https://doi.org/10.1007/s10519-010-9398-1

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Keywords

  • Tuberous sclerosis
  • mTOR
  • Anxiety
  • Learning and memory
  • Behavior
  • Mouse