Tsc mutant embryos feature phenotypic variability and developmental delay, though, which may suggest earlier defects that are compensated for by regulative mechanisms.
One characteristic feature of TSC is the presence of enlarged dysmorphic neurons and giant cells in cortical tubers [ 13].
Although epithelial malignancy is not a common feature of TSC, loss of function of TSC1 has been identified in UC [ 23, 51, 52].
While epithelial malignancy is not a common feature of TSC, studies in this laboratory and others have implicated loss of function of TSC1 in bladder tumorigenesis (17– 17).
Notably, these conditional mouse models displayed most of the distinctive neurological features of TSC.
This strategy allowed us to bypass the lethality of homozygous knockouts and create a novel Tsc2-based model of TSC that recapitulates many features of the human disease in the brain.
The brains of the Tsc2 flox/ko ;hGFAP-Cre mice exhibited many neuropathologic features of human TSC, such as cortical thickening, enlarged cells, lamination defects, heterotopias and abnormal myelination.
Abnormal myelination has recently been found to be another pathologic feature in the brains of TSC patients (58, 59).
These brain malformations are almost universal manifestations in patients with TSC and probably underlie the severe neurological features of epilepsy and autism that are seen in these patients (Crino, 2004; Crino et al., 2006).
They report that deletion of Tsc1 in hippocampal and cortical RGCs during early development results in neurological features that are reminiscent of TSC, some of which were detected in the corresponding Tsc2 mutant mouse that was examined previously.
Despite great progress in the molecular biology of TSC, less is known about the origin and development of phenotypic features of abnormal cell types in the TSC brain.
