the fat mass and obesity associated gene fto functions in the brain to regulate postnatal growth in micefto基因功能相关的脂肪量和肥胖老鼠大脑中调节产后增长.pdf

The Fat Mass and Obesity Associated Gene FTO Functions in the Brain to Regulate Postnatal Growth in Mice 1 2 2 3 3 1,2 Xue Gao , Yong-Hyun Shin , Min Li , Fei Wang , Qiang Tong , Pumin Zhang * 1 Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas, United States of America, 2 Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas, United States of America, 3 Department of Pediatrics, Children’s Nutrition Research Center, Baylor College of Medicine, Houston, Texas, United States of America Abstract FTO (fat mass and obesity associated) was identified as an obesity-susceptibility gene by several independent large-scale genome association studies. A cluster of SNPs (single nucleotide polymorphism) located in the first intron of FTO was found to be significantly associated with obesity-related traits, such as body mass index, hip circumference, and body weight. FTO encodes a protein with a novel C-terminal a-helical domain and an N-terminal double-strand b-helix domain which is conserved in Fe(II) and 2-oxoglutarate-dependent oxygenase family. In vitro, FTO protein can demethylate single-stranded DNA or RNA with a preference for 3-methylthymine or 3-methyluracil. Its physiological substrates and function, however, remain to be defined. Here we report the generation and analysis of mice carrying a conditional deletion allele of Fto. Our results demonstrate that Fto plays an essential role in postnatal growth. The mice lacking Fto completely display immediate postnatal growth retardation with shorter body length, lower body weight, and lower bone mineral density than control mice, but their body compositions are relatively no