The overall goal of these studies is to define the role that gap junctions play in the functions of myelinating, non-myelinating and proliferating Schwann cells in the peripheral nervous system. Because point mutations in Cx32 are responsible for the X-linked form of Charcot-Marie-Tooth syndrome (CMTX), a demyelinating peripheral neuropathy, we are particularly interested in correlated changes in Cx32 expression with myelination in vivo and in culture and in properties of CMTX mutant channels. Because expression of other gap junction proteins (connexins) can be induced in myelinating Schwann cells by nerve injury, we are also interested in the nature of this induction and the changes in Schwann cell behavior when different connexin are expressed. We will apply a broadly based approach to the studies, taking advantage of recently developed animal models deficient in myelin proteins and making use of transfection technology in Schwann cells and cell lines. Specific Aim 1. To compare the functional properties of Schwann cells cultured from myelinated and nonmyelinated nerves of wildtype mice and transgenic mice in which connexin expression is altered. Specific Aim 2. To determine turnover dynamics and transport characteristics of the connexins and their mRNAs that are expressed in myelinating, nonmyelinating and proliferating Schwann cells in wildtype and connexin-altered transgenic mice. Specific Aim 3. To determine the impact of myelin-related genes on gap junction properties using transfected cell lines and Schwann cells cultured from transgenic mice in which myelin-related proteins are altered. Together, these studies should answer major questions regarding basic biology of Schwann cells and the role of gap junctions in physiological and pathophysiological conditions.
|Effective start/end date||2/1/97 → 3/31/03|
- National Institute of Neurological Disorders and Stroke: $319,390.00
- National Institute of Neurological Disorders and Stroke: $326,516.00
- National Institute of Neurological Disorders and Stroke: $310,713.00
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