We have generated a Xenopus laevis transgenic line allowing live imaging and conditional ablation of myelinating oligodendrocytes throughout the central nervous system. In these transgenic pMBP-eGFP-NTR tadpoles the myelin basic protein regulatory sequences, specific to mature oligodendrocytes, are used to drive expression of an eGFP (enhanced green fluorescent protein) reporter fused to the E. coli nitroreductase (NTR) selection enzyme. This enzyme converts the innocuous prodrug metronidazole (MTZ) to a cytotoxin. Using two-photon imaging in vivo, we show that pMBP-eGFP-NTR tadpoles display a graded demyelination response following exposure to MTZ, which depends on the exposure time to the pro-drug. We demonstrate that MTZ-induced cell death was restricted to oligodendrocytes, without detectable axonal damage, as shown by immunolabeling with oligodendrocytes or node of Ranvier markers and electron microscopy. After cessation of MTZ treatment, remyelination proceeded spontaneously, but was strongly accelerated by retinoic acid. Altogether, these features establish the Xenopus pMBP-eGFP-NTR line as a novel in vivo model for the study of demyelination/remyelination processes and for large-scale screens of therapeutic agents promoting myelin repair.
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