The COS-7 Cell In Vitro Paradigm to Study Myelin Proteolipid Protein 1 Gene Mutations

Despite many shortcomings, a reductionist approach using cell culture paradigms to define basic principles underlying disease processes has considerable merit. One example of the utility of this approach is the expression of mutant forms of proteolipid protein 1 (PLP1) in transiently transfected COS-7 cells. In humans, the PLP1 gene is located on the long arm of the X-chromosome and deletion, duplication, or coding region mutations in this gene cause the leukodystrophy, Pelizaeus-Merzbacher disease (PMD). Clinically, PMD is a heterogeneous disease that generally becomes apparent within the first year of life and is associated with hypomyelination in the central or peripheral nervous systems (CNS/PNS), breathing difficulties, poor motor coordination and paraparesis or paraplegia (1 –3 ). From simple beginnings using a transfection paradigm to express missense mutant gene products identified in PMD patients, we have developed an hypothesis to account for the cellular (4 –8 ) and molecular pathogenesis of disease (9 ) and we have made use of several excellent mouse models of PMD to confirm our in vitro findings in vivo (10 ).