title: Different posttranscriptional controls for the human neurofilament light and heavy genes in transgenic mice.
abstract: To investigate the mechanisms regulating neurofilament gene expression, we generated transgenic mice with high copy number of the intact human neurofilament light (NF-L) and heavy (NF-H) genes. Overexpression in transgenic mice of NF-L mRNA from 3- to 5-fold in different regions of the central nervous system (CNS) resulted only in a mild increase of 10-50% in the levels of NF-L proteins. The failure to enhance NF-L protein content was not due to interspecies differences in posttranscriptional NF-L regulation. For instance, based on specific immunodetection, it is estimated that human NF-L proteins composed 80% of total NF-L content in the spinal cord of transgenics. In contrast to the situation with NF-L, the CNS of transgenic mice bearing multiple copies of the human NF-H gene showed comparable increases in the levels of NF-H mRNA and proteins. These results suggest that the NF-L and NF-H genes are subject to different posttranscriptional regulation in the CNS. In vivo labeling of newly synthesized proteins by injection of [35S]methionine in the spinal cords of normal and transgenic mice provided evidence that the posttranscriptional regulation of NF-L expression in the CNS must occur, at least in part, at the level of translation.
authors: Centre for Research in Neuroscience, McGill University, Montreal General Hospital Research Institute, Que, Canada.
authors: L
authors: L
authors: Beaudet
authors: F
authors: F
authors: Côté
authors: D
authors: D
authors: Houle
authors: J P
authors: JP
authors: Julien
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic / Q000378:metabolism; D016900:Neurofilament Proteins / Q000096:biosynthesis* / Q000235:genetics; D014176:Protein Biosynthesis; D011499:Protein Processing, Post-Translational; D012333:RNA, Messenger / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis* / Q000235:genetics; D013045:Species Specificity; D013116:Spinal Cord / Q000378:metabolism
chemical_list: D016900:Neurofilament Proteins; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; C044882:neurofilament protein L; C051774:neurofilament protein H