PUBLICATION
A novel myelin protein zero transgenic zebrafish designed for rapid readout of in vivo myelination
- Authors
- Preston, M.A., Finseth, L.T., Bourne, J.N., Macklin, W.B.
- ID
- ZDB-PUB-190110-5
- Date
- 2019
- Source
- Glia 67(4): 650-667 (Journal)
- Registered Authors
- Macklin, Wendy B.
- Keywords
- in vivo, myelin protein zero, myelination, oligodendrocytes, zebrafish
- MeSH Terms
-
- Sirolimus/pharmacology
- Demyelinating Diseases/genetics*
- Demyelinating Diseases/metabolism
- Demyelinating Diseases/pathology
- Animals, Genetically Modified
- Oligodendroglia/drug effects
- Oligodendroglia/physiology
- Gene Expression Regulation, Developmental/drug effects
- Gene Expression Regulation, Developmental/genetics*
- Spinal Cord/embryology
- Spinal Cord/metabolism
- Neuroglia/metabolism
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- Culture Media, Conditioned/pharmacology
- Animals
- SOXE Transcription Factors/genetics
- SOXE Transcription Factors/metabolism
- Embryo, Nonmammalian
- Myelin P0 Protein/genetics
- Myelin P0 Protein/metabolism*
- Embryonic Stem Cells
- Myelin Basic Protein/genetics
- Myelin Basic Protein/metabolism
- Luminescent Proteins/genetics
- Luminescent Proteins/metabolism
- Green Fluorescent Proteins/genetics
- Green Fluorescent Proteins/metabolism*
- Myelin Sheath/physiology*
- Myelin Sheath/ultrastructure
- Disease Models, Animal
- Immunosuppressive Agents/pharmacology
- Larva
- Zebrafish
- PubMed
- 30623975 Full text @ Glia
Citation
Preston, M.A., Finseth, L.T., Bourne, J.N., Macklin, W.B. (2019) A novel myelin protein zero transgenic zebrafish designed for rapid readout of in vivo myelination. Glia. 67(4):650-667.
Abstract
Demyelination occurs following many neurological insults, most notably in multiple sclerosis (MS). Therapeutics that promote remyelination could slow the neurological decline associated with chronic demyelination; however, in vivo testing of candidate small molecule drugs and signaling cascades known to impact myelination is expensive and labor intensive. Here, we describe the development of a novel zebrafish line which uses the putative promoter of Myelin Protein Zero (mpz), a major structural protein in myelin, to drive expression of Enhanced Green Fluorescent Protein (mEGFP) specifically in the processes and nascent internodes of myelinating glia. We observe that changes in fluorescence intensity in Tg(mpz:mEGFP) larvae are a reliable surrogate for changes in myelin membrane production per se in live larvae following bath application of drugs. These changes in fluorescence are strongly predictive of changes in myelin-specific mRNAs [mpz, 36K and myelin basic protein (mbp)] and protein production (Mbp). Finally, we observe that certain drugs alter nascent internode number and length, impacting the overall amount of myelin membrane synthesized and a number of axons myelinated without significantly changing the number of myelinating oligodendrocytes. These studies demonstrate that the Tg(mpz:mEGFP) reporter line responds effectively to positive and negative small molecule regulators of myelination, and could be useful for identifying candidate drugs that specifically target myelin membrane production in vivo. Combined with high throughput cell-based screening of large chemical libraries and automated imaging systems, this transgenic line is useful for rapid large scale whole animal screening to identify novel myelinating small molecule compounds in vivo.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping