RGD Reference Report - Ciliopathy-associated protein CEP290 modifies the severity of retinal degeneration due to loss of RPGR. - Rat Genome Database

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Ciliopathy-associated protein CEP290 modifies the severity of retinal degeneration due to loss of RPGR.

Authors: Rao, KN  Zhang, W  Li, L  Ronquillo, C  Baehr, W  Khanna, H 
Citation: Rao KN, etal., Hum Mol Genet. 2016 Mar 2. pii: ddw075.
RGD ID: 11537380
Pubmed: PMID:26936822   (View Abstract at PubMed)
PMCID: PMC5062589   (View Article at PubMed Central)
DOI: DOI:10.1093/hmg/ddw075   (Journal Full-text)

Mutations in RPGR (retinitis pigmentosa GTPase regulator) are the most common cause of X-linked RP, a severe blindness disorder. RPGR mutations result in clinically variable disease with early- to late-onset phenotypic presentation. Molecular mechanisms underlying such heterogeneity are unclear. Here we show that phenotypic expression of Rpgr-loss in mice is influenced genetically by the loss of Cep290, a human ciliopathy gene. We found that Rpgrko/Y mice with a heterozygous hypomorphic allele of Cep290 (Cep290rd16/+) but not of a heterozygous null allele of Cep290 (Cep290null/+) or of other ciliopathy genes, Rpgrip1, Nphp1, Nphp4 and Nphp5, exhibit relatively early onset (by 3 months of age) retinal degeneration and dysfunction when compared with the onset at approximately 7 months of age in the Rpgrko/Y mice. We also observed disorganized photoreceptor outer-segment morphology and defective trafficking of opsins in the Rpgrko/Y::Cep290rd16/+ mice. Together with a physical interaction between RPGR and the C-terminal domain of CEP290, our data suggest that RPGR and CEP290 genetically interact and highlight the involvement of hypomorphic alleles of genes as potential modifiers of heterogeneous retinal ciliopathies.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
retinal degeneration onsetISOCep290 (Mus musculus)11537380; 11537380 RGD 
retinal degeneration onsetIGIRpgr (Mus musculus)11537380 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Cep290  (centrosomal protein 290)

Genes (Mus musculus)
Cep290  (centrosomal protein 290)

Genes (Homo sapiens)
CEP290  (centrosomal protein 290)


Additional Information