transforming-growth-factor-beta and 22q11-Deletion-Syndrome

Renal malformations are commonly found among patients carrying a 22q11 deletion which renders loss of Tbx1 gene, an important transcriptional factor implicated in a number of developmental processes. Smad1 is known to interact with Tbx1, but the exact mechanism remains unknown. In this study, we have measured the expression of Tbx1 in both murine and human tissues using RT-PCR, and analyzed its protein product and protein-protein interactions with Western blotting and immunoprecipitation assays. Precipitated proteins were verified with mass spectrometry. As discovered, Tbx1 binds with Hoxd10. Tbx1 and Hoxd10 genes also have similar expression profiles during murine kidney development. Based on homology between mouse and human, we hypothesized that such interaction also exists in human. Through a RNA interference experiment using a human embryonic kidney HEK293 cell line, we demonstrated that TBX1 can alter TGF-β/BMP, an important signaling pathway, through interacting with HOXD10. Above findings may shed light on the mechanism of TBX1 mutations leading to renal malformations found in patients carrying a 22q11 deletion.

Topics: 22q11 Deletion Syndrome; Animals; Animals, Newborn; Bone Morphogenetic Proteins; Embryo, Mammalian; Gene Expression Regulation, Developmental; Gene Knockdown Techniques; HEK293 Cells; Homeodomain Proteins; Humans; Kidney; Mice; Protein Binding; Signal Transduction; T-Box Domain Proteins; Transcription Factors; Transforming Growth Factor beta