Article ; Online: Zebrafish mutants provide insights into Apolipoprotein B functions during embryonic development and pathological conditions.
JCI insight
2021 Volume 6, Issue 13
Abstract: Apolipoprotein B (ApoB) is the primary protein of chylomicrons, VLDLs, and LDLs and is essential for their production. Defects in ApoB synthesis and secretion result in several human diseases, including abetalipoproteinemia and familial ... ...
| Abstract | Apolipoprotein B (ApoB) is the primary protein of chylomicrons, VLDLs, and LDLs and is essential for their production. Defects in ApoB synthesis and secretion result in several human diseases, including abetalipoproteinemia and familial hypobetalipoproteinemia (FHBL1). In addition, ApoB-related dyslipidemia is linked to nonalcoholic fatty liver disease (NAFLD), a silent pandemic affecting billions globally. Due to the crucial role of APOB in supplying nutrients to the developing embryo, ApoB deletion in mammals is embryonic lethal. Thus, a clear understanding of the roles of this protein during development is lacking. Here, we established zebrafish mutants for 2 apoB genes: apoBa and apoBb.1. Double-mutant embryos displayed hepatic steatosis, a common hallmark of FHBL1 and NAFLD, as well as abnormal liver laterality, decreased numbers of goblet cells in the gut, and impaired angiogenesis. We further used these mutants to identify the domains within ApoB responsible for its functions. By assessing the ability of different truncated forms of human APOB to rescue the mutant phenotypes, we demonstrate the benefits of this model for prospective therapeutic screens. Overall, these zebrafish models uncover what are likely previously undescribed functions of ApoB in organ development and morphogenesis and shed light on the mechanisms underlying hypolipidemia-related diseases. |
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| MeSH term(s) | Animals ; Apolipoproteins B/biosynthesis ; Apolipoproteins B/genetics ; Apolipoproteins B/metabolism ; Embryonic Development/genetics ; Endothelial Cells ; Fatty Liver/embryology ; Fatty Liver/genetics ; Goblet Cells ; Intestines/embryology ; Intestines/pathology ; Models, Biological ; Mutation ; Neovascularization, Pathologic/embryology ; Neovascularization, Pathologic/genetics ; Vascular Remodeling/genetics ; Zebrafish ; Zebrafish Proteins/genetics |
| Chemical Substances | Apolipoproteins B ; Zebrafish Proteins |
| Language | English |
| Publishing date | 2021-07-08 |
| Publishing country | United States |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ISSN | 2379-3708 |
| ISSN (online) | 2379-3708 |
| DOI | 10.1172/jci.insight.130399 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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