Master of Science
Dr. Donglin Bai
Gap junctions (GJ) allow direct intercellular communication, and consist of connexins (Cx). In the mammalian central nervous system, oligodendrocytes express Cx29, Cx32 and Cx47, whereas astrocytes express Cx26, Cx30 and Cx43. Cx47/Cx47 GJs couple oligodendrocytes, and Cx47/Cx43 channels are the primary heterotypic GJs at oligodendrocyte/astrocyte junctions. Interestingly, mutations in Cx47 have been linked to central hypomyelinating Pelizaeus Merzbacher-like Disease (PMLD). My aim is to determine the cellular distribution and functional properties of PMLD-associated Cx47 mutants (I46M, G149S, G236R, G236S, M286T, T398I). All mutants were detected at the cell-cell interface. These mutants, except G149S and T398I, showed no electrical coupling in both Cx47/Cx47 and Cx47/Cx43 GJ channels. G149S and T398I formed homotypic and heterotypic channels of apparently normal functions. These results suggest that the tested Cx47 mutants, except G149S and T398I, lead to PMLD likely due to disruption in Cx47/Cx47 and/or Cx47/Cx43 GJ functions in the macroglial network.
Kim, Mi Seong, "The Distribution and Functional Properties of PMLD-Linked CX47 Mutations on CX47/CX47 Homotypic and CX47/CX43 Heterotypic Gap Junctions" (2012). Electronic Thesis and Dissertation Repository. 737.