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PMID:22378290

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Citation

Stiebel-Kalish, H, Reich, E, Rainy, N, Vatine, G, Nisgav, Y, Tovar, A, Gothilf, Y and Bach, M (2012) Gucy2f zebrafish knockdown--a model for Gucy2d-related leber congenital amaurosis. Eur. J. Hum. Genet. 20:884-9

Abstract

Mutations in retinal-specific guanylate cyclase (Gucy2d) are associated with Leber congenital amaurosis-1 (LCA1). Zebrafish offer unique advantages relative to rodents, including their excellent color vision, precocious retinal development, robust visual testing strategies, low cost, relatively easy transgenesis and shortened experimental times. In this study we will demonstrate the feasibility of using gene-targeting in the zebrafish as a model for the photoreceptor-specific GUCY2D-related LCA1, by reporting the visual phenotype and retinal histology resulting from Gucy2f knockdown. Gucy2f zebrafish LCA-orthologous cDNA was identified and isolated by PCR amplification. Its expression pattern was determined by whole-mount in-situ hybridization and its function was studied by gene knockdown using two different morpholino-modified oligos (MO), one that blocks translation of Gucy2f and one that blocks splicing of Gucy2f. Visual function was assessed with an optomotor assay on 6-days-post-fertilization larvae, and by analyzing changes in retinal histology. Gucy2f knockdown resulted in significantly lower vision as measured by the optomotor response compared with uninjected and control MO-injected zebrafish larvae. Histological changes in the Gucy2f-knockdown larvae included loss and shortening of cone and rod outer segments. A zebrafish model of Gucy2f-related LCA1 displays early visual dysfunction and photoreceptor layer dystrophy. This study serves as proof of concept for the use of zebrafish as a simple, inexpensive model with excellent vision on which further study of LCA-related genes is possible.

Links

PubMed PMC3400723 Online version:10.1038/ejhg.2012.10

Keywords

Animals; Animals, Genetically Modified; Disease Models, Animal; Female; Gene Expression Regulation, Developmental; Gene Knockdown Techniques; Guanylate Cyclase/genetics; Leber Congenital Amaurosis/genetics; Leber Congenital Amaurosis/pathology; Male; Receptors, Cell Surface/genetics; Retinal Dystrophies/genetics; Retinal Dystrophies/pathology; Vision, Ocular/genetics; Zebrafish/genetics

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

DANRE:B3DHF2

involved_in

GO:0007601: visual perception

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-MRPHLNO-120926-2

P

Seeded From UniProt

complete

DANRE:B3DHF2

involved_in

GO:0007601: visual perception

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-MRPHLNO-120926-1

P

Seeded From UniProt

complete

DANRE:B3DHF2

involved_in

GO:0035845: photoreceptor cell outer segment organization

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-MRPHLNO-120926-2

P

Seeded From UniProt

complete

DANRE:B3DHF2

involved_in

GO:0035845: photoreceptor cell outer segment organization

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-MRPHLNO-120926-1

P

Seeded From UniProt

complete

DANRE:F1QWF7

involved_in

GO:0007601: visual perception

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-MRPHLNO-120926-2

P

Seeded From UniProt

complete

DANRE:F1QWF7

involved_in

GO:0007601: visual perception

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-MRPHLNO-120926-1

P

Seeded From UniProt

complete

DANRE:F1QWF7

involved_in

GO:0035845: photoreceptor cell outer segment organization

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-MRPHLNO-120926-2

P

Seeded From UniProt

complete

DANRE:F1QWF7

involved_in

GO:0035845: photoreceptor cell outer segment organization

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-MRPHLNO-120926-1

P

Seeded From UniProt

complete

DANRE:Q90WX2

involved_in

GO:0007601: visual perception

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-MRPHLNO-120926-2

P

Seeded From UniProt

complete

DANRE:Q90WX2

involved_in

GO:0007601: visual perception

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-MRPHLNO-120926-1

P

Seeded From UniProt

complete

DANRE:Q90WX2

involved_in

GO:0035845: photoreceptor cell outer segment organization

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-MRPHLNO-120926-2

P

Seeded From UniProt

complete

DANRE:Q90WX2

involved_in

GO:0035845: photoreceptor cell outer segment organization

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-MRPHLNO-120926-1

P

Seeded From UniProt

complete


See also

References

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