Tsc mutant embryos feature phenotypic variability and developmental delay, though, which may suggest earlier defects that are compensated for by regulative mechanisms.
In children, tumor cells with neural progenitor-like features have been isolated from medulloblastomas and ependymomas [25], and TSCs have been well characterized from a few cases of low- and high-grade gliomas [7], [12].
Subsequently, TSCs have attracted great interest in the photovoltaics field.
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.
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].
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.
Compared with sporadic RCCs, TSC-associated RCCs have unique clinicopathologic features including female predominance, younger age at diagnosis, multiplicity, association with AMLs, 3 recurring histologic patterns, and an indolent clinical course.
