Generation of Transgenic and Gene-Targeted Mouse Models of Movement Disorders

In recent years, human genetic linkage studies have yielded a tremendous amount of information about the genetics of many movement disorders. Pathological states of the brain-region specific neuro degeneration and cytological events such as protein aggregation-are correlated with some disorders. The functions of most implicated proteins in movement disorders are unknown and only speculations of possible functions are gathered from sequence homology analyses. As a result, the mechanisms that these mutant proteins work through to cause the pathology are also largely unknown. Differences between the development of mice and humans could affect the expected phenotype and justify cautionary measures that should be taken when applying mouse findings to humans. The usefulness of a model must be defined partly on the ability of the model to mimic the behavioral phenotype of the disorder as well as the presence of other features that allow further understanding of the disorder at other biological levels. Furthermore, regardless of the initially detected behavioral phenotype, a mouse model can also be introduced into various mouse strains to identify modifiers. Environmental factors that may affect a phenotype or the patho physiology of a model can be tested. Complex interactions among numbers of genes can also be evaluated by crossing several mouse lines. The quantity and type of knowledge that can be extracted from a mouse model depend partly on the inherent nature of the mouse physiology and the changes caused by the genetic alteration. The flexibility and virtually limitless material offered by genetically modified mouse lines ensure that mouse models will continue to play a significant role in the understanding of human disorders.