Cre‐inducible site‐specific recombination in zebrafish oligodendrocytes. Issue 1 (11th October 2016) - Pinzon‐Olejua, Alejandro
Abstract : Background: The conditional Cre/lox system has recently emerged as a valuable tool for studies on both embryonic and adult Zebrafish. Temporal control and site‐specific recombination are achieved by using the ligand‐inducible CreER T2 and administration of the drug tamoxifen (TAM) or its active metabolite, 4‐Hydroxytamoxifen (4‐OHT).Results: Here we report the generation of a transgenic Zebrafish line, which expresses an mCherry‐tagged variant of CreER T2 under the control of the myelin basic protein a ( mbpa ) promoter. Our analysis shows that larval and adult expression of the transgene recapitulates the endogenous mbpa expression pattern in oligodendrocytes. Furthermore, combination with a Cre‐dependent EGFP reporter results in EGFP‐expressing oligodendrocytes in the spinal cord, brain, and optic nerve in TAM‐ or 4‐OHT‐treated larvae and 4‐month‐old fish, but not in untreated controls.Conclusions: The transgenic Zebrafish line Tg(mbpa:mCherry‐T2A‐CreER T2 ) elicits CreER T2 expression specifically in myelinating glia cells. Cre‐inducible targeted recombination of genes in oligodendrocytes will be useful to elucidate cellular and molecular mechanisms of myelination in vivo during development (myelination) and regeneration (remyelination) after injury to the central nervous system (CNS). It will also allow targeted expression and overexpression of genes of interest (transgenes) in oligodendrocytes at defined developmental and adult stages. Developmental Dynamics 246:41–49, 2017 . © 2016 Wiley Periodicals, Inc. Key findings: We created a transgenic zebrafish line which elicits CreERT2 expression specifically in myelinating glia cells. Recombination occurs specifically only after treatment with Tamoxifen in larval and adult stages. This line will be a valuable tool to study myelination and remyelination and allows targeted expression of transgenes.