Regulation of the Human Neurofilament Light and Heavy Genes in Transgenic Mice

Abstract

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.