PUBLICATION
Knockdown of zebrafish lumican gene (ZLUM) causes scleral thinning and increased size of scleral coats
- Authors
- Yeh, L.K., Liu, C.Y., Kao, W.W., Huang, C.J., Hu, F.R., Chien, C.L., and Wang, I.J.
- ID
- ZDB-PUB-100621-26
- Date
- 2010
- Source
- The Journal of biological chemistry 285(36): 28141-28155 (Journal)
- Registered Authors
- Huang, Chang-Jen
- Keywords
- EXTRACELLULAR MATRIX/Connective Tissue, EXTRACELLULAR MATRIX/Glycosaminoglycans, EXTRACELLULAR MATRIX/Keratan, PROTEOGLYCANS Structure, PROTEOGLYCANS Synthesis, Axial myopia, Lumican, Sclera
- MeSH Terms
-
- Amino Acid Sequence
- Animals
- Animals, Genetically Modified
- Cattle
- Chondroitin Sulfate Proteoglycans/chemistry
- Chondroitin Sulfate Proteoglycans/deficiency*
- Chondroitin Sulfate Proteoglycans/genetics*
- Chondroitin Sulfate Proteoglycans/metabolism
- Collagen/metabolism
- Conserved Sequence
- Corneal Stroma/metabolism
- Drug Evaluation, Preclinical
- Gene Expression Regulation
- Gene Knockdown Techniques*
- Humans
- Keratan Sulfate/chemistry
- Keratan Sulfate/deficiency*
- Keratan Sulfate/genetics*
- Keratan Sulfate/metabolism
- Larva/anatomy & histology
- Larva/drug effects
- Mice
- Molecular Sequence Data
- Muscarinic Antagonists/pharmacology
- Myopia/drug therapy
- Organ Size/drug effects
- Organ Size/genetics
- Phylogeny
- Promoter Regions, Genetic/genetics
- RNA, Messenger/genetics
- RNA, Messenger/metabolism
- Rats
- Sclera/anatomy & histology*
- Sclera/metabolism*
- Sclera/pathology
- Sclera/ultrastructure
- Sequence Alignment
- Zebrafish/embryology
- Zebrafish/genetics*
- PubMed
- 20551313 Full text @ J. Biol. Chem.
Citation
Yeh, L.K., Liu, C.Y., Kao, W.W., Huang, C.J., Hu, F.R., Chien, C.L., and Wang, I.J. (2010) Knockdown of zebrafish lumican gene (ZLUM) causes scleral thinning and increased size of scleral coats. The Journal of biological chemistry. 285(36):28141-28155.
Abstract
The lumican gene (Lum), which encodes one of the major keratan sulfate proteoglycans (KSPGs) in the vertebrate cornea and sclera, has been linked to axial myopia in humans. In this study, we chose zebrafish (Danio rerio) as an animal model to elucidate the role of lumican in the development of axial myopia. The zebrafish lumican gene (zLum) spans approximately 4.6 kilobases (kb) of the zebrafish genome. Like human (hLUM) and mouse (mLum), zebrafish Lum (zLum) consists of three exons, two introns, and a TATA boxless promoter at the 5'-flanking region of the transcription initiation site. Sequence analysis of the cDNA predicts that zLum encodes 344 amino acids. zLum shares 51% amino acid sequence identity with human lumican. Similar to hLUM and mLum, zLum mRNA is expressed in the eye as well as in many other tissues, such as brain, muscle and liver. Transgenic zebrafish harboring an Enhanced Green Fluorescent Protein (EGFP) reporter gene construct downstream of a 1.7 kb zLum 5'-flanking region displayed EGFP expression in the cornea and sclera, as well as throughout the body. Down-regulation of zLum expression by antisense zLum morpholinos (MO) manifested ocular enlargement resembling axial myopia due to disruption of the collagen fibril arrangement in the sclera and resulted in scleral thinning. Administration of muscarinic receptor antagonists, e.g., atropine, pirenzepine, effectively subdued the ocular enlargement caused by morpholinos in in vivo zebrafish larvae assays. The observation suggests that zebrafish can be used as an in vivo model for screening compounds in treating myopia.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping