RGD Reference Report - Knockout of ISCA1 causes early embryonic death in rats. - Rat Genome Database

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Knockout of ISCA1 causes early embryonic death in rats.

Authors: Yang, Xinlan  Lu, Dan  Zhang, Xu  Chen, Wei  Gao, Shan  Dong, Wei  Ma, Yuanwu  Zhang, Lianfeng 
Citation: Yang X, etal., Animal Model Exp Med. 2019 Mar 12;2(1):18-24. doi: 10.1002/ame2.12059. eCollection 2019 Mar.
RGD ID: 39131292
Pubmed: PMID:31016283   (View Abstract at PubMed)
PMCID: PMC6431120   (View Article at PubMed Central)
DOI: DOI:10.1002/ame2.12059   (Journal Full-text)


Background: Iron-sulfur cluster assembly 1 (ISCA1) is an iron-sulfur (Fe/S) carrier protein that accepts Fe/S from a scaffold protein and transfers it to target proteins including the mitochondrial Fe/S containing proteins. ISCA1 is also the newly identified causal gene for multiple mitochondrial dysfunctions syndrome (MMDS). However, our knowledge about the physiological function of ISCA1 in vivo is currently limited. In this study, we generated an ISCA1 knockout rat line and analyzed the embryo development.
Methods: ISCA1 knockout rats were generated by replacing the exon1 of ISCA1 gene with the mCherry-Cre fusion gene using CRISPR-Cas9 technology. The ISCA1 expression pattern was analyzed by fluorescence imaging using ISCA1 promotor driven Cre and mCherry expression. The embryonic morphology was examinated by microscope and mitochondrial proteins were tested by Western blot.
Results: An ISCA1 knockout rat line was obtained, which expressed mCherry-Cre fusion protein. Both of the fluorescence images from mCherry and Cre induced mCherry in a reporter rat strain, showing that ISCA1 expressed in most of the tissues in rats. The ISCA1 knockout resulted in abnormal development at 8.5 days, with a significant decrease of NDUFA9 protein and an increase of aconitase 2 (ACO2) in rat embryos.
Conclusion: Deletion of ISCA1 induced early death in rats. ISCA1 affected the expression of key proteins in the mitochondrial respiratory chain complex, suggesting that ISCA1 has an important influence on the respiratory complex and energy metabolism.



Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Isca1Ratabnormal respiratory electron transport chain  IMP  RGD 
Isca1Ratembryonic lethality, complete penetrance  IMP  RGD 
Objects Annotated

Genes (Rattus norvegicus)
Isca1  (iron-sulfur cluster assembly 1)


Additional Information