title: Live imaging of targeted cell ablation in Xenopus: a new model to study demyelination and repair.
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.
authors.affiliation: CNRS UPR 3294, Neurobiology and Development, Université Paris Sud XI, 91405 Orsay, France.
authors.forename: Ferdinand
authors.initials: F
authors.lastname: Kaya
authors.forename: Abdelkrim
authors.initials: A
authors.lastname: Mannioui
authors.forename: Albert
authors.initials: A
authors.lastname: Chesneau
authors.forename: Sowmya
authors.initials: S
authors.lastname: Sekizar
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Maillard
authors.forename: Chantal
authors.initials: C
authors.lastname: Ballagny
authors.forename: Ludivine
authors.initials: L
authors.lastname: Houel-Renault
authors.forename: David
authors.initials: D
authors.lastname: Dupasquier
authors.forename: Odile
authors.initials: O
authors.lastname: Bronchain
authors.forename: Isabelle
authors.initials: I
authors.lastname: Holtzmann
authors.forename: Anne
authors.initials: A
authors.lastname: Desmazieres
authors.forename: Jean-Léon
authors.initials: JL
authors.lastname: Thomas
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Demeneix
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Brophy
authors.forename: Bernard
authors.initials: B
authors.lastname: Zalc
authors.forename: Andre
authors.initials: A
authors.lastname: Mazabraud
mesh_terms: D000818:Animals; D003711:Demyelinating Diseases / Q000473:pathology* / Q000503:physiopathology*; D004195:Disease Models, Animal; D006801:Humans; D036641:Microscopy, Fluorescence, Multiphoton / Q000379:methods*; D009416:Nerve Regeneration / Q000502:physiology*; D014982:Xenopus laevis / Q000033:anatomy & histology* / Q000502:physiology*