Primary Study The Function Of THAP11: A Candidate Gene For Polyglutamine Disorders

Polyglutamine(polyQ) diseases is a kind of neurodegenerative diseases caused by expanded CAG repeats in gene coding region resulting in translation products possessing expanded polyglutamine repeats. At present, a large number of pathogenic genes of polyQ diseases have not been revealed. THAP11 was the interact protein of EDAG1 when we study EDAG1, it belongs to THAP proteins family. The analysis of the construction and polymorphism of THAP11 found that it contains a section of polyglutamine fragment coded by CAG repeats which was very instable and essy to expand. Might THAP11 be a candidate gene for polyglutamine disorders? So, we screen the number of CAG repeats of THAP11 between nomal people and neurodegenerative diseases patients ,we found that THAP11(29Q) was common in the normal, and THAP11(38Q) was too much in the patients. The highly expressing of THAP11 can inhibit cell proliferation. we could primarily confirm THAP11 as a candidate gene for polyglutamine disorders.For futher study of the function of THAP11, we have established the ecdysone-inducible expression system in PC12 cells,and try to research the cytobiology effect of it. In addition,for the reseach of the relationship between THAP11 and polyQ diseases on the level of model organism, we have constructed a series of the THAP11 transgenic Caenorhabditis elegans vectors and created some of the THAP11 transgenic Caenorhabditis elegans. we have found that THAP11(29Q) and THAP11(38Q) was different in the time and nuber of the formation of protein aggregations in the PC12 cells. The expression of THAP11 can cause the arresting of cell cycle in G0/G1, with the expressing of THAP11, the PC12 cell proliferation can be inhibited. Investigating the mechanism of these effects we found that the expression of c-myc,which was important in cell proliferation, was decreased along with the expression of THAP11,but this effect was not associated with the number of polyQs. These THAP11 transgenic Caenorhabditis elegans vectors can be used to create transgenic Caenorhabditis elegans succefully.It can provide the model for the futher study.