Tuberous sclerosis complex (TSC) is a dominant tumor suppressor disorder caused 
by mutations in either TSC1 or TSC2. TSC causes substantial neuropathology, 
often leading to autism spectrum disorders (ASDs) in up to 60% of patients. The 
anatomic and neurophysiologic links between these two disorders are not well 
understood. We have generated and characterized a novel TSC mouse model with 
Purkinje cell specific Tsc2 loss. These Tsc2f/-;Cre mice exhibit progressive 
Purkinje cell degeneration. Since loss of Purkinje cells is a well reported 
postmortem finding in patients with ASD, we conducted a series of behavior tests 
to asses if Tsc2f/-;Cre mice displayed autistic-like deficits. Tsc2f/-;Cre mice 
demonstrated increased repetitive behavior as assessed with marble burying 
activity. Using the three chambered apparatus to asses social behavior, we found 
that Tsc2f/-;Cre mice showed behavioral deficits, exhibiting no preference 
between a stranger mouse and an inanimate object, or between a novel and a 
familiar mouse. We also detected social deficits in Tsc2f/f;Cre mice, suggesting 
that Purkinje cell pathology is sufficient to induce ASD-like behavior. 
Importantly, social behavior deficits were prevented with rapamycin treatment. 
Altogether, these results demonstrate that loss of Tsc2 in Purkinje cells in a 
Tsc2-haploinsufficient background leads to autistic-like behavioral deficits. 
These studies provide compelling evidence that Purkinje cell loss and/or 
dysfunction may be an important link between TSC and ASD as well as a general 
anatomic phenomenon that contributes to the ASD phenotype.