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XB-ART-45943
J Neurosci September 12, 2012; 32 (37): 12885-95.
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Live imaging of targeted cell ablation in Xenopus: a new model to study demyelination and repair.

Kaya F , Mannioui A , Chesneau A , Sekizar S , Maillard E , Ballagny C , Houel-Renault L , Dupasquier D , Bronchain O , Holtzmann I , Desmazieres A , Thomas JL , Demeneix BA , Brophy PJ , Zalc B , Mazabraud A .


Abstract
Live imaging studies of the processes of demyelination and remyelination have so far been technically limited in mammals. We have thus generated a Xenopus laevis transgenic line allowing live imaging and conditional ablation of myelinating oligodendrocytes throughout the CNS. In these transgenic pMBP-eGFP-NTR tadpoles the myelin basic protein (MBP) regulatory sequences, specific to mature oligodendrocytes, are used to drive expression of an eGFP (enhanced green fluorescent protein) reporter fused to the Escherichia 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 oligodendrocyte ablation in response to MTZ, which depends on the exposure time to MTZ. MTZ-induced cell death was restricted to oligodendrocytes, without detectable axonal damage. 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.

PubMed ID: 22973012
PMC ID: PMC3460536
Article link: J Neurosci
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: mbp nkx2-2 ntsr1 pgrmc2
GO keywords: oligodendrocyte development [+]

Disease Ontology terms: multiple sclerosis

Article Images: [+] show captions
References [+] :
Ainger, Transport and localization elements in myelin basic protein mRNA. 1997, Pubmed