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To facilitate live imaging of demyelina-tion and remyelination, we have generated aXenopus laevis transgenic line,MBP-GFP-NTR, allowing con-ditional ablation of myelinating oligodendrocytes. In this line, the proximal portion of mouse myelin basic protein (MBP) regulatory sequence, specific to mature myelin-forming oligodendrocytes, drives the expression of a transgene protein formed by the GFP reporter fused to the Escherichia colinitroreductase (NTR) selection enzyme. The NTR enzyme converts the innocuous pro-drug metronidazole (MTZ) to a cytotoxin. The demyeli-nation response ofMBP-GFP-NTR tadpoles to MTZ is followed by spontaneous remyelination after cessation of MTZ treatment. Thanks to the transparency of tadpoles, these events can be monitoredin vivo by two-photon imaging and easily quantified on a simple fluorescence macroscope. We have used theMBP-GFP-NTR model to screenin vivo molecules favoring remyelination. At the end of MTZ-induced demyelination, tadpoles were switched to water containing the compounds to be tested. After 3 days of treatment remyelination was assayed by counting the number of GFP+ oligodendrocytes per optic nerve. Using Crispr/Cas9 strategy, the target of the candidate molecule can be easily deleted in theMBP-GFP-NTR line to examine the mechanism of action of the candidate molecule. Therefore theXenopus laevis transgenic line,MBP-GFP-NTR, allowing conditional ablation of myelinating oligodendrocytes, constitutes a new medium-throughput screening platform for myelin repair therapeutics in demyelinating diseases.