Fto and Postnatal Growth Figure 7. Neural-specific Fto knockout mice are growth retarded. (A) The breeding scheme to generate neural-specific Fto knockout mice. (B) Western blot analysis of different tissues of FtoN+ and FtoND mice. (C) Body weights of 7-day-old FtoN+/+, FtoN+/D and FtoND/D pups. For each genotype (FtoN+/+/FtoN+/D/FtoND/D), n = 17/7/9 (male), and 14/7/8 (female). (D) Growth curves of male and female FtoN+ and FtoND mice. For each genotype (FtoN+/FtoND), n = 30/25(male), and 24/20(female). (E, F) Body length (E) and femur bone mineral density (F) of 16-week-old FtoN+ and FtoND mice measured by DEXA. For each genotype (FtoN+/FtoND), n = 19/21(male), 19/17(female). (G) Relative serum IGF-1 levels of 4-week-old FtoN+ and FtoND mice. For each genotype (FtoN+/FtoND), n = 6/6(male), and n = 5/4(female). Statistical analyses were performed by one-way ANOVA (C) or unpaired t-test (D–G). **P,0.01. All values are mean 6 s.e.m. doi:10.1371/journal.pone.0014005.g007 found no clear association between obesity-related SNPs and the FTO mRNA expression levels in adipose tissue and skeletal muscle [41–43]. In fact, both negative and positive correlations have been observed [41,43], complicating the effort in decipher- ing the effect of these SNPs on FTO expression. Recently, heterozygous loss-of-function FTO mutations have been identified in both lean and obese humans [37]. Moreover, patients carrying homozygous loss-of-function mutations in FTO show severe growth retardation and multiple malformations, but no record of obesity [44]. Thus, the growth retardation phenotype is shared between human and mouse when FTO is not functional, indicating a primary function of FTO in the regulation of linear PLoS ONE | www.plosone.org 9 November 2010 | Volume 5 | Issue 11 | e14005