Dominantly inherited demyelinating neuropathies, known as Charcot-Marie-Tooth disease type 1 (CMT1), are among the most common inherited neurological diseases. CMT1 is caused by mutations in one of several genes that are expressed by myelinating Schwann cells, including PMP22, MPZ, and GJB1. In this grant, we will perform the following:
Specific aim 1 : To delineate the genotype-phenotype correlations which affect disease severity in CMTX.
Specific Aim 2 : To test the hypothesis that gain of function mutations in Cx32, identified by an abnormal subcellular localization of the protein, or abnormalities on gap junction by dye transfer, producethe most severe CMTX phenotype.
Specific Aim 3 : To distinguish between gain of function and loss offunction mechanisms participating in the pathogenesis of CMTX, by generating and comparing Gjbl1knockin mice bearing mutations causing severe neuropathy with Gjb1 null mice.
| Ferguson, Toby A; Scherer, Steven S (2012) Neuronal cadherin (NCAD) increases sensory neurite formation and outgrowth on astrocytes. Neurosci Lett 522:108-12 |
| Ahn, Meejin; Lee, Jonathan; Gustafsson, Andreas et al. (2008) Cx29 and Cx32, two connexins expressed by myelinating glia, do not interact and are functionally distinct. J Neurosci Res 86:992-1006 |
| Orthmann-Murphy, Jennifer L; Abrams, Charles K; Scherer, Steven S (2008) Gap junctions couple astrocytes and oligodendrocytes. J Mol Neurosci 35:101-16 |
| Sargiannidou, Irene; Ahn, Meejin; Enriquez, Alan D et al. (2008) Human oligodendrocytes express Cx31.3: function and interactions with Cx32 mutants. Neurobiol Dis 30:221-33 |
| Orthmann-Murphy, Jennifer L; Enriquez, Alan D; Abrams, Charles K et al. (2007) Loss-of-function GJA12/Connexin47 mutations cause Pelizaeus-Merzbacher-like disease. Mol Cell Neurosci 34:629-41 |
| Orthmann-Murphy, Jennifer L; Freidin, Mona; Fischer, Esther et al. (2007) Two distinct heterotypic channels mediate gap junction coupling between astrocyte and oligodendrocyte connexins. J Neurosci 27:13949-57 |
| Yum, Sabrina W; Zhang, Junxian; Valiunas, Virginijus et al. (2007) Human connexin26 and connexin30 form functional heteromeric and heterotypic channels. Am J Physiol Cell Physiol 293:C1032-48 |
| Menichella, Daniela M; Majdan, Marta; Awatramani, Rajeshwar et al. (2006) Genetic and physiological evidence that oligodendrocyte gap junctions contribute to spatial buffering of potassium released during neuronal activity. J Neurosci 26:10984-91 |
| LeBlanc, Scott E; Jang, Sung-Wook; Ward, Rebecca M et al. (2006) Direct regulation of myelin protein zero expression by the Egr2 transactivator. J Biol Chem 281:5453-60 |
| Berti, Caterina; Nodari, Alessandro; Wrabetz, Lawrence et al. (2006) Role of integrins in peripheral nerves and hereditary neuropathies. Neuromolecular Med 8:191-204 |
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