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XB-ART-54061
Mult Scler. July 1, 2017; 1352458517721355.

The Xenopus tadpole: An in vivo model to screen drugs favoring remyelination.

Mannioui A , Vauzanges Q , Fini JB , Henriet E , Sekizar S , Azoyan L , Thomas JL , Pasquier DD , Giovannangeli C , Demeneix B , Lubetzki C , Zalc B .


Abstract
In multiple sclerosis, development of screening tools for remyelination-promoting molecules is timely. A Xenopus transgenic line allowing conditional ablation of myelinating oligodendrocytes has been adapted for in vivo screening of remyelination-favoring molecules. In this transgenic, the green fluorescent protein reporter is fused to E. coli nitroreductase and expressed specifically in myelinating oligodendrocytes. Nitroreductase converts the innocuous pro-drug metronidazole to a cytotoxin. Spontaneous remyelination occurs after metronidazole-induced demyelinating responses. As tadpoles are transparent, these events can be monitored in vivo and quantified. At the end of metronidazole-induced demyelination, tadpoles were screened in water containing the compounds tested. After 72 h, remyelination was assayed by counting numbers of oligodendrocytes per optic nerve. Among a battery of molecules tested, siponimod, a dual agonist of sphingosine-1-phosphate receptor 1 and 5, was among the most efficient favoring remyelination. Crispr/cas9 gene editing showed that the promyelinating effect of siponimod involves the sphingosine-1-phosphate receptor 5. This Xenopus transgenic line constitutes a simple in vivo screening platform for myelin repair therapeutics. We validated several known promyelinating compounds and demonstrated that the strong remyelinating efficacy of siponimod implicates the sphingosine-1-phosphate receptor 5.

PubMed ID: 28752787
Article link: Mult Scler.

Genes referenced: s1pr5



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