RGD Reference Report - Cisd2 deficiency drives premature aging and causes mitochondria-mediated defects in mice. - Rat Genome Database

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Cisd2 deficiency drives premature aging and causes mitochondria-mediated defects in mice.

Authors: Chen, YF  Kao, CH  Chen, YT  Wang, CH  Wu, CY  Tsai, CY  Liu, FC  Yang, CW  Wei, YH  Hsu, MT  Tsai, SF  Tsai, TF 
Citation: Chen YF, etal., Genes Dev. 2009 May 15;23(10):1183-94. doi: 10.1101/gad.1779509.
RGD ID: 10045601
Pubmed: PMID:19451219   (View Abstract at PubMed)
PMCID: PMC2685531   (View Article at PubMed Central)
DOI: DOI:10.1101/gad.1779509   (Journal Full-text)

CISD2, the causative gene for Wolfram syndrome 2 (WFS2), is a previously uncharacterized novel gene. Significantly, the CISD2 gene is located on human chromosome 4q, where a genetic component for longevity maps. Here we show for the first time that CISD2 is involved in mammalian life-span control. Cisd2 deficiency in mice causes mitochondrial breakdown and dysfunction accompanied by autophagic cell death, and these events precede the two earliest manifestations of nerve and muscle degeneration; together, they lead to a panel of phenotypic features suggestive of premature aging. Our study also reveals that Cisd2 is primarily localized in the mitochondria and that mitochondrial degeneration appears to have a direct phenotypic consequence that triggers the accelerated aging process in Cisd2 knockout mice; furthermore, mitochondrial degeneration exacerbates with age, and the autophagy increases in parallel to the development of the premature aging phenotype. Additionally, our Cisd2 knockout mouse work provides strong evidence supporting an earlier clinical hypothesis that WFS is in part a mitochondria-mediated disorder; specifically, we propose that mutation of CISD2 causes the mitochondria-mediated disorder WFS2 in humans. Thus, this mutant mouse provides an animal model for mechanistic investigation of Cisd2 protein function and help with a pathophysiological understanding of WFS2.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Wolfram syndrome 2  ISOCisd2 (Mus musculus)10045601; 10045601 RGD 
Wolfram syndrome 2  IMP 10045601 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Cisd2  (CDGSH iron sulfur domain 2)

Genes (Mus musculus)
Cisd2  (CDGSH iron sulfur domain 2)

Genes (Homo sapiens)
CISD2  (CDGSH iron sulfur domain 2)


Additional Information