Analysis of pathological cascade in CAG repeat disease

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Recently, the list of diseases characterized by trinucleotide repeat expansions has grown rapidly. So far, the following diseases have been reported to be caused by CAG repeat expansion : spinal and bulbar muscular atrophy (SBMA), Huntington's diseases, SCA1, dentatorubral-pallidoluysian atrophy (DRPLA), MJD,and SCA2. The expanded CAG repeat is located within the coding regions of the genes of patients with these diseases. We have revealed that the abnormal gene product is actually translated in HD,and DRPLA,suggesting that the expanded polyglutamine stretch plays a role in the pathomechanism of these diseases.In this study, we have investigated the function of gene products by searching the related molecules with the gene product. The following results were obtained.1) We identified the DRPLA gene product expression in lymphoblastoid cells2) Analyzing DRPLA gene products with the two-dimensional gel electrophoresis, we found the isoforms of DRPLA proteins which are phosphorylated.3) We obtained two binding proteins with DRPLA gene product using two-hybrid system.4) We identified the MJD gene products and reported their expression.5) We showed the association of HD gene products with microtubules.