title: The fat mass and obesity associated gene FTO functions in the brain to regulate postnatal growth in mice.
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 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Xue
authors.initials: X
authors.lastname: Gao
authors.forename: Yong-Hyun
authors.initials: YH
authors.lastname: Shin
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Tong
authors.forename: Pumin
authors.initials: P
authors.lastname: Zhang
mesh_terms: D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D000818:Animals; D015153:Blotting, Western; D001835:Body Weight / Q000235:genetics* / Q000502:physiology; D015519:Bone Density / Q000502:physiology; D001921:Brain / Q000254:growth & development / Q000378:metabolism*; D004041:Dietary Fats / Q000008:administration & dosage; D005260:Female; D018507:Gene Expression Regulation, Developmental; D020022:Genetic Predisposition to Disease; D006130:Growth Disorders / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009765:Obesity / Q000209:etiology / Q000235:genetics / Q000503:physiopathology; D011506:Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D004041:Dietary Fats; D011506:Proteins; C524916:FTO protein, mouse; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO