Various conditional knockouts of Tsc1 or Tsc2 have been used to determine cell types and brain regions involved in the different components of TSC. Mice with Tsc1 deficiency in cerebellar Purkinje cells by the expression of L7-Cre in either Tsc1flox/+ or Tsc1flox/flox display ASD-like behaviors (Tsai et al., 2012). Moreover, conditional knockout of Tsc1 in Purkinje cells leads to decreased cell numbers, increased soma size, increased spine density, and lower spontaneous spiking rates in these cells (Tsai et al., 2012). Another group crossed Pcp2-Cre mice with Tsc2flox/− mice, resulting in homozygous deletion of Tsc2 in Purkinje cells and heterozygous deletion of Tsc2 in all other cells, and report exacerbated ASD-like phenotypes (Reith et al., 2013). One may argue that the latter study doesn’t make use of the high construct validity provided by the haploinsufficiency of the TSC mouse model. However, loss of heterozygosity (LOH) occurs in a cell-specific manner in TSC (Crino, 2013) and it is possible that LOH in Purkinje cells accounts for some of the ASD symptoms in human TSC patients, but more work needs to be done
