| First Author | Millecamps S | Year | 2007 |
| Journal | J Neurosci | Volume | 27 |
| Issue | 18 | Pages | 4947-56 |
| PubMed ID | 17475803 | Mgi Jnum | J:121331 |
| Mgi Id | MGI:3709808 | Doi | 10.1523/JNEUROSCI.5299-06.2007 |
| Citation | Millecamps S, et al. (2007) Conditional NF-L transgene expression in mice for in vivo analysis of turnover and transport rate of neurofilaments. J Neurosci 27(18):4947-56 |
| abstractText | We generated mice with doxycycline control of a human neurofilament light (NF-L) transgene in the context of the absence (tTA;hNF-L;NF-L(-/-)) or presence (tTA;hNF-L;NF-L(+/-)) of endogenous mouse NF-L proteins. Doxycycline treatment caused the rapid disappearance of human NF-L (hNF-L) mRNA in tTA;hNF-L mice, but the hNF-L proteins remained with a half-life of 3 weeks in the brain. In the sciatic nerve, the disappearance of hNF-L proteins after doxycycline treatment occurred in synchrony along the sciatic nerve, suggesting a proteolysis of NF proteins along the entire axon. The presence of permanent NF network in tTA;hNF-L;NF-L(+/-) mice further stabilized and extended longevity of hNF-L proteins by several months. Surprisingly, after cessation of doxycycline treatment, there was no evidence of leading front of newly synthesized hNF-L proteins migrating into sciatic nerve axons devoid of NF structures. The hNF-L proteins detected at weekly intervals reappeared and accumulated in synchrony at similar rate along nerve segments, a phenomenon consistent with a fast hNF-L transport into axons. We estimated the hNF-L transport rate to be of approximately 10 mm/d in axons devoid of NF structures based on the use of an adenovirus encoding tet-responsive transcriptional activator to transactivate the hNF-L transgene in hypoglossal motor neurons. These results provide in vivo evidence that the stationary NF network in axons is a key determinant of half-life and transport rate of NF proteins. |
