Differential Gene Expression in a Mouse Model of Huntington's Disease.
Carnazza, Kathryn E.
- Huntington's disease (HD) is a fatal genetic neurodegenerative disorder. It is inherited in an autosomal dominant fashion. HD typically manifests itself in middle age, though in some cases, symptoms appear earlier. Patients with HD suffer from a gross motor dysfunction, neuronal atrophy, cognitive impairments, psychiatric disturbances, and metabolic disruption, among other symptoms. Death follows ... read moreanywhere from 10-25 years after the onset of symptoms. The causative mutation of this disease, a CAGn expansion in the HTT gene, was discovered more than 17 years ago. This gene codes for huntingtin, which is essential for both development and survival of many organisms. However, the exact molecular workings of this disease are still unknown. Partially due to the paucity of this information, there is no cure for the disease, and treatment consists only of controlling certain symptoms to improve quality of life. Research is focused on elucidating the pathways and molecules that contribute to disease progression. Much of this research utilizes animal models of HD, including a mouse model with a CAGn expansion inserted into the murine homologue of HTT. A collaborative study with the German Mouse Clinic with the aim of better understanding Huntington's disease pathogenesis led to the identification of a number of differentially expressed genes in brain and liver tissues of a knock-in mouse model of the disorder. In this study, we sought to further characterize the expression of a selection of these genes both knock-in and wild-type mice. We employed TaqMan real-time PCR assays to investigate the previously observed changes in expression. The data we collected for a majority of the genes are inconclusive. However, our preliminary results are encouraging for two of the genes, Prok1 and Nfkbia. We found Prok1 to be significantly downregulated in the knock-in mice, and observed downregulation in Nfkbia in the knock-in mice as well. These two genes provide potential avenues for new hypotheses about the disease process in HD.read less