The cytoarchitecture of animal cells is comprised of three principal components: actin filaments, microtubules, and intermediate filaments. While the functions of actin arrays and microtubules are well documented, no companion function for most intermediate filaments is known, and the difficulty in using genetic approaches in higher eukaryotes has precluded directs analysis of the consequences of disruption of intermediate filament synthesis and assembly. Using genes engineered to encode wildtype or mutant polypeptides of neurofilaments, the intermediate filament of nerve cells, we propose here to use a combination of DNA transfection and transgenic mice to identify under what conditions the neurofilament proteins NF-L,NF-M and NF-H can coassembly with the other classes of intermediate filaments and identify the domains of the subunits that are necessary for normal filament assembly. Moreover, we want to determine what features of NF genes are responsible for neuronal specific expression and we want to identify the molecular events responsible for our finding that expression of the enogenous NF-M gene is activated by transfection of NF-L genes into cultured fibroblasts. Finally, with regard to determining the in vivo function(s) contributed by NF, we and our proteins of NF directly correlates with the diameters of mammalian nerve fibers.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
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Molecular Cytology Study Section (CTY)
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Johns Hopkins University
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McMahon, Moira A; Prakash, Thazha P; Cleveland, Don W et al. (2018) Chemically Modified Cpf1-CRISPR RNAs Mediate Efficient Genome Editing in Mammalian Cells. Mol Ther 26:1228-1240
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