Fig. 1 | Nature Communications

Fig. 1

From: Distinct molecular pathways mediate Mycn and Myc-regulated miR-17-92 microRNA action in Feingold syndrome mouse models

Fig. 1

Generation of mouse models of Feingold syndrome. a Forelimbs of wildtype control (Ctrl), Mycn Knockout (Prx1-Cre:Mycnfl/fl, Mycn cKO), Mir17-92 knockout (Prx1-Cre:Mir17-92fl/fl, 17 KO), and Mir17-92 and Mir106b-25 doubly conditional knockout (Prx1-Cre:Mir17-92fl/fl:Mir106b-25−/−, 17 dKO) mice at postnatal day (P) 16. 17 KO mutants exhibit mild brachydactyly in the fifth digit (double-headed arrows). Cutaneous syndactyly (arrows) and severe brachydactyly are presented in 17 dKO and Mycn cKO mice. Scale bar, 0.5 cm. b Alizarin red and alcian blue staining of the forelimb and magnified views of the fifth digit of corresponding mice in a. 17 KO mutants show shortening of the middle phalanx (M) (brackets) of the fifth digit. 17 dKO and Mycn cKO mutants show severe brachymesophalangy and the absence of the middle phalanx of the fifth digit (arrows). c Alizarin red and alcian blue staining of the skull of corresponding mice in a. Mycn cKO, 17 KO, and 17 dKO mice show microcephaly and a frontal bone ossification defect (arrows). Scale bar, 1 cm. d Quantification of the length of the fifth M and fifth metacarpal bone (5th MC) and the ratio of 5th M to 5th MC. Values are expressed as mean ± SE (n = 5 in each group, *p < 0.001 vs. Ctrl). ND, not detected. e Relative expression of five miRNAs encoded in the Mir17-92 gene in limb bud mesenchymal cells isolated from Mycn cKO embryos at embryonic day 14.5. (relative to control littermate samples, n = 5 each group, *<0.001 vs. Ctrl at every time point). f Hindlimbs of wildtype Ctrl, Mycn cKO, and Mycn Knockout overexpressing Mir17-92 (Prx1-Cre:Mycnfl/fl:Mir17-92Tg, Mycn cKO:17 Tg) (upper panels) and alizarin red and alcian blue staining of the hindlimbs of corresponding genotypes (bottom panels). Mir17-92 overexpression partially rescues the skeletal defects of Mycn cKO mutants. Cutaneous syndactyly (white arrows) and shortening of the fifth digit in Mycn cKO mutants are rescued by overexpression of Mir17-92 whereas fused fourth and fifth metatarsal bones still remain (bottom panels). Scale bar, 0.5 cm

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