Increased Levels of Anxiety-related Behaviors in a Tsc2 Dominant Negative Transgenic Mouse Model of Tuberous Sclerosis
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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.
KeywordsTuberous sclerosis mTOR Anxiety Learning and memory Behavior Mouse
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.
- Govindarajan B, Brat DJ, Csete M, Martin WD, Murad E, Litani K, Cohen C, Cerimele F, Nunnelley M, Lefkove B et al (2005) Transgenic expression of dominant negative tuberin through a strong constitutive promoter results in a tissue-specific tuberous sclerosis phenotype in the skin and brain. J Biol Chem 280:5870–5874PubMedCrossRefGoogle Scholar
- Meikle L, Talos DM, Onda H, Pollizzi K, Rotenberg A, Sahin M, Jensen FE, Kwiatkowski DJ (2007) A mouse model of tuberous sclerosis: neuronal loss of Tsc1 causes dysplastic and ectopic neurons, reduced myelination, seizure activity, and limited survival. J Neurosci 27:5546–5558PubMedCrossRefGoogle Scholar