关键词：神经学；遗传学；突变；蛋白
摘 要：Dystonia is the 3rd most common movement disorder, and some forms are brought on by stress. Investigators have not yet succeeded in making a genetic mouse model of dystonia by conventional approaches. A novel strategy was designed to combine three mutant mouse strains together by breeding to reduce the expression of a protein known to be mutated in an inherited human dystonia triggered by stress. There were problems with one of the mouse strains, however, which lost one of its genetic modifications, and a different strategy was adopted. This was successful, and a mouse with the desired dystonic symptoms was obtained. It has two mutations, one a dominantly inherited gene with 100% penetrance, and the other a strain-specific modifier gene that controls how strong the symptoms are. These genes were mapped to two loci on two different chromosomes. The behavior of the mouse was extensively characterized. Swim stress brought about very severe symptoms, but the mice fully recovered to a moderate dystonic baseline. As planned, electrophysiology and electromyography were performed, showing the co-contraction of opposing muscles, the hallmark of dystonia.