PUBLICATION
neb: a zebrafish model of nemaline myopathy due to nebulin mutation
- Authors
- Telfer, W.R., Nelson, D.D., Waugh, T., Brooks, S.V., and Dowling, J.J.
- ID
- ZDB-PUB-120105-28
- Date
- 2012
- Source
- Disease models & mechanisms 5(3): 389-396 (Journal)
- Registered Authors
- Waugh, Trent
- Keywords
- none
- MeSH Terms
-
- Actin Cytoskeleton/pathology
- Actin Cytoskeleton/ultrastructure
- Amino Acid Sequence
- Animals
- Disease Models, Animal
- Embryo, Nonmammalian/metabolism
- Embryo, Nonmammalian/ultrastructure
- Humans
- Larva
- Molecular Sequence Data
- Motor Activity/physiology
- Muscle Contraction/physiology
- Muscle Proteins/chemistry
- Muscle Proteins/genetics*
- Muscle, Skeletal/pathology
- Muscle, Skeletal/physiopathology
- Muscle, Skeletal/ultrastructure
- Mutation/genetics*
- Myopathies, Nemaline/genetics*
- Myopathies, Nemaline/pathology
- Myopathies, Nemaline/physiopathology
- Phenotype
- RNA Processing, Post-Transcriptional/genetics
- Zebrafish/embryology
- Zebrafish/genetics*
- Zebrafish Proteins/chemistry
- Zebrafish Proteins/genetics*
- PubMed
- 22159874 Full text @ Dis. Model. Mech.
Citation
Telfer, W.R., Nelson, D.D., Waugh, T., Brooks, S.V., and Dowling, J.J. (2012) neb: a zebrafish model of nemaline myopathy due to nebulin mutation. Disease models & mechanisms. 5(3):389-396.
Abstract
Nemaline myopathy is one of the most common and severe non-dystrophic muscle diseases of childhood. Patients typically present in infancy with hypotonia, weakness, delayed motor development, and bulbar and respiratory difficulties. Mutations in six different genes are associated with nemaline myopathy, with nebulin mutations being the most common. No treatments or disease-modifying therapies have been identified for this disease. One of the major barriers to treatment development is the lack of models amenable to rapid and coordinated testing of potential therapeutic strategies. To overcome this barrier, we have characterized the first zebrafish model of nemaline myopathy. This model, termed neb, harbors a recessive mutation in the nebulin gene that results in decreased Nebulin protein levels, a severe motor phenotype and premature lethality. In addition to impaired motor function, neb zebrafish exhibit many of the features associated with human nemaline myopathy. These include impaired force generation, altered thin filament length and the presence of specific histopathological changes, including the formation of nemaline bodies. In summary, neb zebrafish mirror the genetic, clinical and pathological aspects of nemaline myopathy due to NEB mutation, and thus are an excellent model for future therapy development for this devastating disorder.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping