Ph.D. Projects
Pathogenesis of Myelin Protein Zero Neuropathies in transgenic mice?
One of our central interests is the molecular genetics of hereditary demyelinating neuropathies. We have established several animal models of Charcot Marie Tooth (CMT) neuropathies in order to address two problems: what genetic mechanisms (gain versus loss of function) can account for the wide diversity of neuropathic phenotypes associated with mutations in Myelin Protein Zero (MPZ; CMT1B) and what cell biological pathomechanisms underlie altered function.
One of these mutant mice, MpzS63del, manifests demyelination caused by the unfolded protein response (UPR) to the mutant P0S63del. A Ph.D. project is available to study how mediators of UPR produce demyelination. Preliminary data suggests that the UPR perturbs differentiation of myelin forming Schwann cells, lipid synthesis, translational regulation of the stoichiometry of myelin proteins, ER associated degradation, and proteasome efficiency. The project includes genetic manipulation of these processes in S63del mutant mice to explore not only how they generate pathology, but also how they participate in normal myelin formation.
