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Generation and characterization of a tamoxifen‐inducible MGAT2 knockout mouse
Author(s) -
Banh Taylor,
Gao Yu,
Nelson David W,
Yen MeiI,
Yen ChiLiang Eric
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.794.1
Subject(s) - knockout mouse , biology , tamoxifen , endocrinology , medicine , gene , exon , gene expression , biochemistry , genetics , cancer , breast cancer
Acyl CoA: monoacylglycerol acyltransferase (MGAT) 2 catalyzes the resynthesis of triacylglycerol during intestinal fat absorption. Mice lacking the encoding gene (Mogat2−/−) are protected from obesity and associated metabolic disorders induced by high‐fat feeding, despite absorbing normal quantities of fat. To determine if MGAT2 inactivation in adulthood is a feasible strategy for managing metabolic disorders, we generated and characterized a tamoxifen‐inducible knockout model using the Cre/loxP system, which enables inactivation of MGAT2 during different life stages. Mice with loxP sites flanking exon 2 of the Mogat2 gene (floxed mice) exhibited expression and activity similar to wildtypes. Floxed mice expressing the inducible‐Cre (UBC‐Cre mice) also had similar MGAT2 expression and showed no differences in growth. After tamoxifen treatment at 2–3 months of age, these UBC‐Cre mice had no MGAT2 expression like Mogat2−/− mice (which do not have a functional Mogat2 gene since fertilization), confirming the efficiency of MGAT2 inactivation. In preliminary short‐term feeding studies, UBC‐Cre mice grew similarly to wildtype mice on low‐fat diets but are protected from weight‐gain induced by high‐fat feeding. These data suggest that inhibiting MGAT2 in adulthood may prove useful in treating obesity. Funding: NIH 5T32DK007665.