The fat mass and obesity associated gene FTO functions in the brain to regulate postnatal growth in mice.
The fat mass and obesity associated gene FTO functions in the brain to regulate postnatal growth in mice.
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DOI：
10.1371/journal.pone.0014005
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发表时间：
2010-11-16
期刊：
影响因子：
3.7
通讯作者：
Zhang P
中科院分区：
文献类型：
--
作者：
Gao X;Shin YH;Li M;Wang F;Tong Q;Zhang P
FTO （fat mass and obesity associated）是几个独立的大规模基因组关联研究确定的肥胖易感基因。位于FTO第一个内含子上的一组snp（单核苷酸多态性）被发现与肥胖相关的性状（如体重指数、臀围和体重）显著相关。FTO编码了一个具有新的c端α-螺旋结构域和n端双链β-螺旋结构域的蛋白，该蛋白在铁（II）和2-氧戊二酸依赖加氧酶家族中保守。在体外，FTO蛋白可以使单链DNA或RNA去甲基化，并优先选择3-甲基胸腺嘧啶或3-甲基尿嘧啶。然而，其生理基础和功能仍有待确定。在这里，我们报道了携带Fto条件缺失等位基因的小鼠的产生和分析。我们的结果表明，Fto在出生后的生长中起着至关重要的作用。完全缺乏Fto的小鼠在出生后立即出现生长迟缓，体长较短，体重较轻，骨密度较低，但体成分相对正常。与生长迟缓一致，Fto突变小鼠血清IGF-1水平降低。此外，尽管Fto普遍表达，但其在神经系统中的特异性缺失导致与全身缺失相似的表型，这表明Fto在中枢神经系统中起调节出生后生长的作用。
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 α-helical domain and an N-terminal double-strand β-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 normal. Consistent with the growth retardation, the Fto mutant mice have reduced serum levels of IGF-1. Moreover, despite the ubiquitous expression of Fto, its specific deletion in the nervous system results in similar phenotypes as the whole body deletion, indicating that Fto functions in the central nerve system to regulate postnatal growth.
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影响因子：
158.5
作者：
Cecil, Joanne E.;Tavendale, Roger;Palmer, Colin N. A.
通讯作者：
Palmer, Colin N. A.
影响因子：
5.8
作者：
Hakanen, Maarit;Raitakari, Olli T.;Ronnemaa, Tapani
通讯作者：
Ronnemaa, Tapani
通过小鼠和人 FTO 对单链 DNA 和 RNA 中的 3-甲基胸腺嘧啶和 3-甲基尿嘧啶进行氧化去甲基化。
影响因子：
3.5
作者：
Jia, Guifang;Yang, Cai-Guang;Yang, Shangdong;Jian, Xing;Yi, Chengqi;Zhou, Zhiqiang;He, Chuan
通讯作者：
He, Chuan
DOI：
10.1126/science.1151710
发表时间：
2007-11-30
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Gerken T;Girard CA;Tung YC;Webby CJ;Saudek V;Hewitson KS;Yeo GS;McDonough MA;Cunliffe S;McNeill LA;Galvanovskis J;Rorsman P;Robins P;Prieur X;Coll AP;Ma M;Jovanovic Z;Farooqi IS;Sedgwick B;Barroso I;Lindahl T;Ponting CP;Ashcroft FM;O'Rahilly S;Schofield CJ
通讯作者：
Schofield CJ
影响因子：
56.9
作者：
Frayling, Timothy M.;Timpson, Nicholas J.;McCarthy, Mark I.
通讯作者：
McCarthy, Mark I.