Regulation of the Human Neurofilament Light and Heavy Genes in Transgenic Mice
Using the transgenic mouse approach, we investigated the mechanisms that regulate expression of the human neurofilament light (NF-L) and heavy (NF-H) genes. Both human NF-L and NF-H genes are expressed in a tissue-specific fashion in transgenic mice. For the NF-L gene, various constructs have been tested in transgenic mice to define regulatory regions contributing to neuronal expression. Unexpectedly, this analysis demonstrated the presence of intragenic elements in the NF-L gene that confer cell-type specific regulation on the basal activity of the proximal NF-L promoter. Moreover, the examination of transgenic mice bearing a high-copy number of the NF-L gene revealed the existence of a translational control impeding overexpression of NF-L in CNS neurons. Unlike the NF-L gene, overexpression of the human NF-H gene in transgenic mice was not impeded by the existence of such posttranscriptional controls.
KeywordsMigration Neuropathy Polypeptide Polyacrylamide Neurol
Unable to display preview. Download preview PDF.
- Hoffman PN, Lasek RJ (1975) The slow component of axonal transport. Identification of major structural polypeptides of the axon and their generality among mammalian neurons. J Cell Biol 66:351–366Google Scholar
- Krimperfort PJ, Schaart G, Pieper FR, Ramaekers FC, Guypers HT, Van den Neuvel RM, Vree Egberts WT, Van Eys GY, Berns A, Bloemendal H (1988) Tissue-specific expression of a vimentin-desmin hybrid gene in transgenic mice. EMBO J 7:941–947Google Scholar
- Yachnis AT, Trojanowski JQ, Memmo M, Schlaepfer WW (1988) Expression of neurofilament proteins in the hypertrophic granule cells of Lhermitte-Duclos disease: An explanation for the mass effect and the myelination of parallel fibers in the disease state. J Neuropathol Exp Neurol 47:206–216PubMedCrossRefGoogle Scholar