PUBLICATION
Reduction in fragile X related 1 protein causes cardiomyopathy and muscular dystrophy in zebrafish
- Authors
- van't Padje, S., Chaudhry, B., Severijnen, L.A., van der Linde, H.C., Mientjes, E.J., Oostra, B.A., and Willemsen, R.
- ID
- ZDB-PUB-090807-7
- Date
- 2009
- Source
- The Journal of experimental biology 212(Pt 16): 2564-2570 (Journal)
- Registered Authors
- Keywords
- fxr1, morpholino, knockdown, cardiomyopathy, muscular dystrophy
- MeSH Terms
-
- 5' Untranslated Regions/genetics
- Animals
- Base Sequence
- Cause of Death
- Embryonic Development
- Fish Diseases/genetics*
- Fragile X Mental Retardation Protein/genetics*
- Fragile X Syndrome/genetics
- Fragile X Syndrome/veterinary
- Heart/physiopathology
- In Situ Hybridization
- Mice
- Muscle, Skeletal/pathology
- Muscle, Skeletal/physiology
- Muscular Dystrophy, Animal/genetics*
- Myocardium/metabolism
- Protein Biosynthesis
- RNA, Messenger/genetics
- RNA-Binding Proteins/genetics
- Zebrafish/embryology
- Zebrafish/genetics*
- Zebrafish/growth & development
- PubMed
- 19648401 Full text @ J. Exp. Biol.
Citation
van't Padje, S., Chaudhry, B., Severijnen, L.A., van der Linde, H.C., Mientjes, E.J., Oostra, B.A., and Willemsen, R. (2009) Reduction in fragile X related 1 protein causes cardiomyopathy and muscular dystrophy in zebrafish. The Journal of experimental biology. 212(Pt 16):2564-2570.
Abstract
Lack of the FMR1 gene product causes fragile X syndrome, the commonest inherited cause of mental impairment. We know little of the roles that fragile X related (FXR) gene family members (FMR1, FXR2 and FXR1) play during embryonic development. Although all are expressed in the brain and testis, FXR1 is the principal member found in striated and cardiac muscle. The Fxr1 knockout mice display a striated muscle phenotype but it is not known why they die shortly after birth; however, a cardiac cause is possible. The zebrafish is an ideal model to investigate the role of fxr1 during development of the heart. We have carried out morpholino knockdown of fxr1 and have demonstrated abnormalities of striated muscle development and abnormal development of the zebrafish heart, including failure of looping and snapping of the atrium from its venous pole. In addition, we have measured cardiac function using high-speed video microscopy and demonstrated a significant reduction in cardiac function. This cardiac phenotype has not been previously described and suggests that fxr1 is essential for normal cardiac form and function.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping