|Education||BS, Seoul National University|
Transforming growth factor beta (TGF-β) signaling is one of the major regulatory signaling pathways of cellular processes such as cell growth, cell differentiation and cell apoptosis. There are several diseases that associated with dysregulated TGF-β signaling. Marfan syndrome (MFS) and Loeys-Dietz syndrome (LDS) are the most typical genetic disorder with the syndromic presentations of aneurysm mediated by dysregulated TGF-β signaling. Shprintzen-Goldberg syndrome (SGS) has considerable phenotypic overlap with MFS and LDS in the cardiovascular, craniofacial and skeletal systems. Furthermore, unlike MFS and LDS, the SGS patients show intellectual disability (ID). Recently, heterozygous missense point mutations in the proto-oncogene SKI, a known repressor of TGF-β activity discovered in the genome of SGS patient as a potential causative factor of SGS by using a combination of whole exome and Sanger sequencing.
However, it is still unclear what kind of genetic mechanism of the SKI mutations causes SGS and what the functional consequence of the SKI mutations is. We hypothesize a mouse model which includes the heterozygous missense point mutations in an endogenous SKI allele recapitulates manifestations of SGS and overexpression of normal or mutant SKI protein in specific origin derived tissues can give us the clue to understand the disease mechanism of SGS.
Therefore, my thesis projects are 1) developing disease mouse model of SGS and 2) developing conditional transgenic mouse model that overexpress normal or mutant SKI protein postnatally. Overall research goal is to understand the functional consequence of the SKI mutations by using mouse model and define the genetic mechanism of the mutation of ski gene in SGS.
Key Words: Shprintzen-Goldberg Syndrome (SGS), TGF-β signaling, SKI, Disease mouse model