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Lack of de novo phosphatidylinositol synthesis leads to endoplasmic reticulum stress and hepatic steatosis in cdipt-deficient zebrafish


ABSTRACT: cdipt is an essential gene in the synthesis of phosphatidylinositol (PtdIns) in the zebrafish, Danio rerio. The zebrafish mutant cdipt^hi559Tg (ZL782) carries a retroviral insertion which inactivates cdipt. Homozygous mutants exhibit hepatocellular endoplasmic reticulum (ER) stress and non-alcoholic fatty liver disease (NAFLD) pathologies at 5 days post fertilization (dpf). This study reveals a novel link between PtdIns, ER stress, and steatosis. We compared whole animal gene expression profiles of hi559 mutant larvae with phenotypically wild type larvae from a heterozygote incross in triplicate.

ORGANISM(S): Danio rerio

SUBMITTER: Carsten Stuckenholz 

PROVIDER: E-GEOD-17711 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Lack of de novo phosphatidylinositol synthesis leads to endoplasmic reticulum stress and hepatic steatosis in cdipt-deficient zebrafish.

Thakur Prakash C PC   Stuckenholz Carsten C   Rivera Marcus R MR   Davison Jon M JM   Yao Jeffrey K JK   Amsterdam Adam A   Sadler Kirsten C KC   Bahary Nathan N  

Hepatology (Baltimore, Md.) 20110502 2


<h4>Unlabelled</h4>Hepatic steatosis is the initial stage of nonalcoholic fatty liver disease (NAFLD) and may predispose to more severe hepatic disease, including hepatocellular carcinoma. Endoplasmic reticulum (ER) stress has been recently implicated as a novel mechanism that may lead to NAFLD, although the genetic factors invoking ER stress are largely unknown. During a screen for liver defects from a zebrafish insertional mutant library, we isolated the mutant cdipthi559Tg/+ (hi559). CDIPT is  ...[more]

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