Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3PT, UK.
MRC Harwell Institute, Mammalian Genetics Unit and Mary Lyon Centre, Harwell Campus, Oxfordshire, OX11 0RD, UK.
Biochim Biophys Acta Mol Basis Dis. 2018 Mar;1864(3):843-850. doi: 10.1016/j.bbadis.2017.11.027. Epub 2017 Dec 2.
The Fto gene locus has been linked to increased body weight and obesity in human population studies, but the role of the actual FTO protein in adiposity has remained controversial. Complete loss of FTO protein in mouse and of FTO function in human patients has multiple and variable effects. To determine which effects are due to the ability of FTO to demethylate mRNA, we genetically engineered a mouse with a catalytically inactive form of FTO. Our results demonstrate that FTO catalytic activity is not required for normal body composition although it is required for normal body size and viability. Strikingly, it is also essential for normal bone growth and mineralization, a previously unreported FTO function.
Fto 基因座与人群研究中体重增加和肥胖有关，但 FTO 蛋白在肥胖中的实际作用仍存在争议。在小鼠中完全缺失 FTO 蛋白和在人类患者中缺失 FTO 功能会产生多种不同的影响。为了确定哪些影响是由于 FTO 去甲基化 mRNA 的能力，我们通过基因工程构建了一种 FTO 催化失活形式的小鼠。我们的结果表明，尽管 FTO 催化活性对于正常的身体组成是必需的，但对于正常的身体大小和活力来说并非必需。引人注目的是，它对于正常的骨骼生长和矿化也是必不可少的，这是之前未报道过的 FTO 功能。
