PUBLICATION
The Zebrafish fade out Mutant: A Novel Genetic Model for Hermansky-Pudlak Syndrome
- Authors
- Bahadori, R., Rinner, O., Schonthaler, H.B., Biehlmaier, O., Makhankov, Y.V., Rao, P., Jagadeeswaran, P., and Neuhauss, S.C.
- ID
- ZDB-PUB-061010-4
- Date
- 2006
- Source
- Investigative ophthalmology & visual science 47(10): 4523-4531 (Journal)
- Registered Authors
- Bahadori, Ronja, Biehlmaier, Oliver, Jagadeeswaran, Pudur, Neuhauss, Stephan, Rinner, Oliver
- Keywords
- none
- MeSH Terms
-
- Hermanski-Pudlak Syndrome/genetics*
- Hermanski-Pudlak Syndrome/pathology
- Whole Blood Coagulation Time
- Melanosomes/genetics*
- Melanosomes/pathology
- Animals
- Zebrafish/genetics*
- Radiation Hybrid Mapping
- Hypopigmentation/genetics*
- Genetic Linkage
- Electroretinography
- Glutamate-Ammonia Ligase/metabolism
- Fluorescent Antibody Technique, Indirect
- Photoreceptor Cells, Vertebrate/physiology
- Photoreceptor Cells, Vertebrate/ultrastructure
- Models, Genetic*
- Mutation*
- Apoptosis
- Genes, Recessive
- In Situ Nick-End Labeling
- Pigment Epithelium of Eye/pathology
- Synaptosomal-Associated Protein 25/metabolism
- Retinal Diseases/genetics*
- Retinal Diseases/pathology
- Nystagmus, Optokinetic/physiology
- PubMed
- 17003448 Full text @ Invest. Ophthalmol. Vis. Sci.
Citation
Bahadori, R., Rinner, O., Schonthaler, H.B., Biehlmaier, O., Makhankov, Y.V., Rao, P., Jagadeeswaran, P., and Neuhauss, S.C. (2006) The Zebrafish fade out Mutant: A Novel Genetic Model for Hermansky-Pudlak Syndrome. Investigative ophthalmology & visual science. 47(10):4523-4531.
Abstract
PURPOSE: To characterize retinal morphology and visual system function in the zebrafish mutant fade out (fad) and to establish the mutant as a lower vertebrate model for Hermansky-Pudlak syndrome (HPS). METHODS: Retinal morphology of fad larvae was examined between 3 and 9 days postfertilization (dpf) by standard histology, transmission electron microscopy, and immunohistochemistry examination. Apoptotic cells were visualized by TdT-mediated dUTP nick-end labeling (TUNEL) staining. Visual system function was probed by electroretinography and behavioral assessment by optokinetic response measurements. Blood clotting was evaluated by time to occlusion testing of blood vessels as an arterial thrombosis assay. The chromosomal location of fad was determined by simple sequence-length polymorphism mapping. Genomic fragments of candidate genes were cloned by standard molecular techniques and mapped to the zebrafish genome by radiation hybrid mapping. RESULTS: Mutant fad larvae are hypopigmented and show structural defects in the outer retina. Melanosomes of these larvae in the retinal pigment epithelium are hypopigmented, generally smaller, and progressively reduced in number compared to nonmutant larvae. Progressive microvilli protrusions into the photoreceptor cell layer are not detectable, and photoreceptor outer segments get shorter and are misaligned. Photoreceptors subsequently undergo apoptosis, with a peak of cell death at 6 dpf. Electrical responses of the retina and visual performance are severely reduced. Blood clotting is prolonged in mutant fad larvae. Genomic mapping of fad reveals distinct genomic positions of the mutant gene from known human HPS genes. CONCLUSIONS: The fad mutant shows syndromic defects in pigmentation, outer retinal structure and function, and blood clotting. This syndrome is characteristic of Hermansky-Pudlak syndrome (HPS), making fad a novel genetic model of HPS. The gene does not cosegregate with the known human HPS genes, suggesting a novel molecular cause of HPS.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping