RGD Reference Report - Development of a Pde6b Gene Knockout Rat Model for Studies of Degenerative Retinal Diseases. - Rat Genome Database

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Development of a Pde6b Gene Knockout Rat Model for Studies of Degenerative Retinal Diseases.

Authors: Yeo, Joon Hyung  Jung, Bok Kyoung  Lee, Heuiran  Baek, In-Jeoung  Sung, Young Hoon  Shin, Hae-Sol  Kim, Hong Kyung  Seo, Kyoung Yul  Lee, Joo Yong 
Citation: Yeo JH, etal., Invest Ophthalmol Vis Sci. 2019 Apr 1;60(5):1519-1526. doi: 10.1167/iovs.18-25556.
RGD ID: 40924664
Pubmed: PMID:31009522   (View Abstract at PubMed)
DOI: DOI:10.1167/iovs.18-25556   (Journal Full-text)

Purpose: To describe the phenotypes of a newly developed Pde6b-deficient rat model of retinal degeneration.
Methods: Pde6b knockout rats were produced by CRISPR-Cpf1 technology. Pde6b knockout rats were evaluated for ocular abnormalities by comparison with wild-type eyes. Eyes were imaged using fundus photography and optical coherence tomography (OCT), stained by hematoxylin and eosin (H&E), and examined by TUNEL assay. Finally, eyes were functionally assessed by electroretinograms (ERGs).
Results: Pde6b knockout rats exhibited visible photoreceptor degeneration at 3 weeks of postnatal age. The fundus appearance of mutants was notable for pigmentary changes, vascular attenuation with an irregular vascular pattern, and outer retinal thinning, which resembled retinitis pigmentosa (RP) in humans. OCT showed profound retinal thinning in Pde6b knockout rats; the outer nuclear layer (ONL) was significantly thinner in Pde6b knockout rats, with relative preservation of the inner retina at 3 weeks of postnatal age. H&E staining confirmed extensive degeneration of the ONL, beginning at 3 weeks of postnatal age; no ONL remained in the retina by 16 weeks of postnatal age. Retinal sections of Pde6b knockout rats were highly positive for TUNEL, specifically in the ONL. In ERGs, Pde6b knockout rats showed no detectable a- or b-waves at 8 weeks of postnatal age.
Conclusions: The Pde6b knockout rat exhibits photoreceptor degeneration. It may provide a better model for experimental therapy for RP because of its slower progression and larger anatomic architecture than the corresponding mouse model. Further studies in this rat model may yield insights into effective therapies for human RP.

Disease Annotations    

Gene Ontology Annotations    

Biological Process

Phenotype Annotations    
Objects Annotated

Genes (Rattus norvegicus)
Pde6b  (phosphodiesterase 6B)
Pde6bem1Baek  (phosphodiesterase 6B; Cpf1-CRISPR induced mutant1, Baek)

Genes (Mus musculus)
Pde6b  (phosphodiesterase 6B, cGMP, rod receptor, beta polypeptide)

Genes (Homo sapiens)
PDE6B  (phosphodiesterase 6B)

SD-Pde6bem1Baek  (NA)

Additional Information