000K utf8 1100 2023$c2023-03-02 1500 eng 2050 urn:nbn:de:gbv:27-dbt-20230405-142842-005 2051 10.3390/ijms24054815 3000 Heydeck, Dagmar 3010 Kakularam, Kumar R. 3010 Kuhn, Hartmut 3010 Liehr, Thomas 3010 Poulain, Philippe 3010 Rothe, Michael 3010 Ufer, Christoph 4000 Functional Characterization of Transgenic Mice Overexpressing Human 15-Lipoxygenase-1 (ALOX15) under the Control of the aP2 Promoter [Heydeck, Dagmar] 4060 24 Seiten 4209 Arachidonic acid lipoxygenases (ALOX) have been implicated in the pathogenesis of inflammatory, hyperproliferative, neurodegenerative, and metabolic diseases, but the physiological function of ALOX15 still remains a matter of discussion. To contribute to this discussion, we created transgenic mice (aP2-ALOX15 mice) expressing human ALOX15 under the control of the aP2 (adipocyte fatty acid binding protein 2) promoter, which directs expression of the transgene to mesenchymal cells. Fluorescence in situ hybridization and whole-genome sequencing indicated transgene insertion into the E1-2 region of chromosome 2. The transgene was highly expressed in adipocytes, bone marrow cells, and peritoneal macrophages, and ex vivo activity assays proved the catalytic activity of the transgenic enzyme. LC-MS/MS-based plasma oxylipidome analyses of the aP2-ALOX15 mice suggested in vivo activity of the transgenic enzyme. The aP2-ALOX15 mice were viable, could reproduce normally, and did not show major phenotypic alterations when compared with wildtype control animals. However, they exhibited gender-specific differences with wildtype controls when their body-weight kinetics were evaluated during adolescence and early adulthood. The aP2-ALOX15 mice characterized here can now be used for gain-of-function studies evaluating the biological role of ALOX15 in adipose tissue and hematopoietic cells. 4950 https://doi.org/10.3390/ijms24054815$xR$3Volltext$534 4950 https://nbn-resolving.org/urn:nbn:de:gbv:27-dbt-20230405-142842-005$xR$3Volltext$534 4961 https://www.db-thueringen.de/receive/dbt_mods_00056756 5051 610 5550 atherosclerosis 5550 eicosanoids 5550 inflammation 5550 inflammation 5550 oxidative stress 5550 polyenoic fatty acids