RGD Reference Report - Caspase-7 ablation modulates UPR, reprograms TRAF2-JNK apoptosis and protects T17M rhodopsin mice from severe retinal degeneration. - Rat Genome Database

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Caspase-7 ablation modulates UPR, reprograms TRAF2-JNK apoptosis and protects T17M rhodopsin mice from severe retinal degeneration.

Authors: Choudhury, S  Bhootada, Y  Gorbatyuk, O  Gorbatyuk, M 
Citation: Choudhury S, etal., Cell Death Dis. 2013 Mar 7;4:e528. doi: 10.1038/cddis.2013.34.
RGD ID: 8548491
Pubmed: PMID:23470535   (View Abstract at PubMed)
PMCID: PMC3613823   (View Article at PubMed Central)
DOI: DOI:10.1038/cddis.2013.34   (Journal Full-text)

The UPR is activated in the mouse retina expressing misfolded T17M rhodopsin (RHO) during autosomal dominant retinitis pigmentosa (ADRP) progression. Therefore, the goal of this study is to validate the UPR-induced caspase-7 as a new therapeutic target that modulates the UPR, reduces the level of apoptosis and protects the ADRP retina from retinal degeneration and light-induced damage. Mice were analyzed using ERG, SD-OCT and histology to determine the role of caspase-7 ablation. The results of these experiments demonstrate the significant preservation of photoreceptors and their function in T17M RHO CASP-7 retinas from P30 to P90 compared with control mice. These mice were also protected from the light-induced decline in the ERG responses and apoptosis. The RNA and protein analyses of T17M RHO+Csp7-siRNA, Tn+Csp7-siRNA 661W cells and T17M RHO CASP-7 retinas revealed that caspase-7 ablation reprograms the UPR and reduces JNK-induced apoptosis. This reduction is believed to occur through the downregulation of the mTOR and Hif1a proteins. In addition, decline in activated PARP1 was detected in T17M RHO CASP-7 retina. Altogether, our findings indicate that the targeting of caspase-7 in T17M RHO mice could be a feasible therapeutic strategy for advanced stages of ADRP.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
retinitis pigmentosa  ISOCasp7 (Mus musculus)8548491; 8548491 RGD 
retinitis pigmentosa  IMP 8548491 RGD 
retinitis pigmentosa  IAGP 8548491DNA:missense mutation: :p.T17M (human)RGD 
retinitis pigmentosa  ISORHO (Homo sapiens)8548491; 8548491DNA:missense mutation: :p.T17M (human)RGD 

Phenotype Annotations    Click to see Annotation Detail View

Manual Human Phenotype Annotations - RGD

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Rod-cone dystrophy  IAGP 8548491DNA:missense mutation:cds:p.T17MRGD 
Objects Annotated

Genes (Rattus norvegicus)
Casp7  (caspase 7)
Rho  (rhodopsin)

Genes (Mus musculus)
Casp7  (caspase 7)
Rho  (rhodopsin)

Genes (Homo sapiens)
CASP7  (caspase 7)
RHO  (rhodopsin)


Additional Information