ZFIN ID: ZDB-PUB-190110-5
A novel myelin protein zero transgenic zebrafish designed for rapid readout of in vivo myelination
Preston, M.A., Finseth, L.T., Bourne, J.N., Macklin, W.B.
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:
  • Animals
  • Animals, Genetically Modified
  • Culture Media, Conditioned/pharmacology
  • Demyelinating Diseases/genetics*
  • Demyelinating Diseases/metabolism
  • Demyelinating Diseases/pathology
  • Disease Models, Animal
  • Embryo, Nonmammalian
  • Embryonic Stem Cells
  • Gene Expression Regulation, Developmental/drug effects
  • Gene Expression Regulation, Developmental/genetics*
  • Green Fluorescent Proteins/genetics
  • Green Fluorescent Proteins/metabolism*
  • Immunosuppressive Agents/pharmacology
  • Larva
  • Luminescent Proteins/genetics
  • Luminescent Proteins/metabolism
  • Myelin Basic Protein/genetics
  • Myelin Basic Protein/metabolism
  • Myelin P0 Protein/genetics
  • Myelin P0 Protein/metabolism*
  • Myelin Sheath/physiology*
  • Myelin Sheath/ultrastructure
  • Neuroglia/metabolism
  • Oligodendroglia/drug effects
  • Oligodendroglia/physiology
  • SOXE Transcription Factors/genetics
  • SOXE Transcription Factors/metabolism
  • Sirolimus/pharmacology
  • Spinal Cord/embryology
  • Spinal Cord/metabolism
  • Zebrafish
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
PubMed: 30623975 Full text @ Glia
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.
ADDITIONAL INFORMATION