دورية أكاديمية

A novel myelin protein zero transgenic zebrafish designed for rapid readout of in vivo myelination.

التفاصيل البيبلوغرافية
العنوان: A novel myelin protein zero transgenic zebrafish designed for rapid readout of in vivo myelination.
المؤلفون: Preston MA; Department of Cell and Developmental Biology, University of Colorado School of Medicine, Aurora, Colorado., Finseth LT; Department of Cell and Developmental Biology, University of Colorado School of Medicine, Aurora, Colorado., Bourne JN; Department of Cell and Developmental Biology, University of Colorado School of Medicine, Aurora, Colorado., Macklin WB; Department of Cell and Developmental Biology, University of Colorado School of Medicine, Aurora, Colorado.
المصدر: Glia [Glia] 2019 Apr; Vol. 67 (4), pp. 650-667. Date of Electronic Publication: 2019 Jan 09.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Wiley-Liss Country of Publication: United States NLM ID: 8806785 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1098-1136 (Electronic) Linking ISSN: 08941491 NLM ISO Abbreviation: Glia Subsets: MEDLINE
أسماء مطبوعة: Publication: New York, NY : Wiley-Liss
Original Publication: New York : Alan R. Liss, Inc., c1988-
مواضيع طبية MeSH: Demyelinating Diseases/*genetics , Gene Expression Regulation, Developmental/*genetics , Green Fluorescent Proteins/*metabolism , Myelin P0 Protein/*metabolism , Myelin Sheath/*physiology, Animals ; Animals, Genetically Modified ; Culture Media, Conditioned/pharmacology ; Demyelinating Diseases/metabolism ; Demyelinating Diseases/pathology ; Disease Models, Animal ; Embryo, Nonmammalian ; Embryonic Stem Cells ; Gene Expression Regulation, Developmental/drug effects ; Green Fluorescent Proteins/genetics ; Immunosuppressive Agents/pharmacology ; Larva ; Luminescent Proteins/genetics ; Luminescent Proteins/metabolism ; Myelin Basic Protein/genetics ; Myelin Basic Protein/metabolism ; Myelin P0 Protein/genetics ; 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 ; Red Fluorescent Protein
مستخلص: 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.
(© 2019 Wiley Periodicals, Inc.)
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معلومات مُعتمدة: NS078386 United States NS NINDS NIH HHS; FG 2078-A-1 United Kingdom Multiple Sclerosis Society; FG 2078-A-1RG 5334-A-12 United Kingdom Multiple Sclerosis Society; R21 NS078386 United States NS NINDS NIH HHS; RG 5334-A-12 United Kingdom Multiple Sclerosis Society
فهرسة مساهمة: Keywords: in vivo; myelin protein zero; myelination; oligodendrocytes; zebrafish
المشرفين على المادة: 0 (Culture Media, Conditioned)
0 (Immunosuppressive Agents)
0 (Luminescent Proteins)
0 (Myelin Basic Protein)
0 (Myelin P0 Protein)
0 (SOXE Transcription Factors)
0 (Zebrafish Proteins)
0 (enhanced green fluorescent protein)
0 (sox10 protein, zebrafish)
147336-22-9 (Green Fluorescent Proteins)
W36ZG6FT64 (Sirolimus)
تواريخ الأحداث: Date Created: 20190110 Date Completed: 20190611 Latest Revision: 20231213
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC6555554
DOI: 10.1002/glia.23559
PMID: 30623975
قاعدة البيانات: MEDLINE
الوصف
تدمد:1098-1136
DOI:10.1002/glia.23559