Extended Data Fig. 4: SIRT6 deficiency resulted in a pan-tissue developmental delay.

a, Micro-computed tomography of the hand (left), distal femoral trabecular (middle) bones and relative bone density (right) of wild-type and SIRT6^−/− newborn, and wild-type 2- and 4-month-old fetal, monkeys. Arrows point to the missing bone connections in the hands of the SIRT6^−/− monkeys and wild-type fetuses. Scale bars, 2.5 mm. n = 3 monkeys. b, Haematoxylin and eosin staining of the superficial intestinal epithelia from a wild-type newborn and 4-month-old fetus, and a SIRT6^−/− newborn monkey. Arrows point to regions of immature intestine epithelium in the tissues of the fetus and the SIRT6^−/− monkey. Scale bar, 75 μm. n = 3 images (Vectra automated quantitative pathology imaging system) per monkey. c, Haematoxylin and eosin staining shows the absence of subcutaneous fat in a newborn SIRT6^−/− monkey and wild-type 4-month-old fetus. In the tissue of the wild-type infant, the subcutaneous fat is circled with a dashed black line. Scale bar, 100 μm. n = 3 images (Vectra automated quantitative pathology imaging system) per monkey. d–f, Haematoxylin and eosin staining of the indicated tissues in newborn SIRT6^−/− monkeys and 2-month-old fetal, 4-month-old fetal and newborn wild-type monkeys. d, Kidney, n ≥ 80 glomeruli per monkey; e, liver, n ≥ 9 images per monkey; f, lung, n = 9 images per monkey. In the bar graph, the grey dashed lines represent the average value of the wild-type fetuses. Scale bar, 100 μm. Data are mean ± s.e.m.; P values were determined by two-sided Student’s t-test (a), one-way ANOVA followed by Holm–Sidak’s multiple comparisons test (b–f).

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