Lipidomic QTL in Diversity Outbred mice identifies a novel function for α/β hydrolase domain 2 (Abhd2) as an enzyme that metabolizes phosphatidylcholine and cardiolipin.

Autor: Price TR; Department of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin, United States of America., Stapleton DS; Department of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin, United States of America., Schueler KL; Department of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin, United States of America., Norris MK; Department of Nutrition and Integrative Physiology, University of Utah, Salt Lake City, Utah, United States of America., Parks BW; Department of Nutritional Sciences, University of Wisconsin-Madison, Madison, Wisconsin, United States of America., Yandell BS; Department of Statistics, University of Wisconsin-Madison, Madison, Wisconsin, United States of America., Churchill GA; The Jackson Laboratory, Bar Harbor, Maine, United States of America., Holland WL; Department of Nutrition and Integrative Physiology, University of Utah, Salt Lake City, Utah, United States of America., Keller MP; Department of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin, United States of America., Attie AD; Department of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
Jazyk: angličtina
Zdroj: PLoS genetics [PLoS Genet] 2023 Jul 31; Vol. 19 (7), pp. e1010713. Date of Electronic Publication: 2023 Jul 31 (Print Publication: 2023).
DOI: 10.1371/journal.pgen.1010713
Abstrakt: We and others have previously shown that genetic association can be used to make causal connections between gene loci and small molecules measured by mass spectrometry in the bloodstream and in tissues. We identified a locus on mouse chromosome 7 where several phospholipids in liver showed strong genetic association to distinct gene loci. In this study, we integrated gene expression data with genetic association data to identify a single gene at the chromosome 7 locus as the driver of the phospholipid phenotypes. The gene encodes α/β-hydrolase domain 2 (Abhd2), one of 23 members of the ABHD gene family. We validated this observation by measuring lipids in a mouse with a whole-body deletion of Abhd2. The Abhd2KO mice had a significant increase in liver levels of phosphatidylcholine and phosphatidylethanolamine. Unexpectedly, we also found a decrease in two key mitochondrial lipids, cardiolipin and phosphatidylglycerol, in male Abhd2KO mice. These data suggest that Abhd2 plays a role in the synthesis, turnover, or remodeling of liver phospholipids.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2023 Price et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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