Fig. 1: Dactylaplasia limb malformation is caused by an unmethylated MusD insertion at the Fgf8 locus. | Nature Genetics

Fig. 1: Dactylaplasia limb malformation is caused by an unmethylated MusD insertion at the Fgf8 locus.

From: Enhancer adoption by an LTR retrotransposon generates viral-like particles, causing developmental limb phenotypes

Fig. 1

a, Scheme of the 7,486 bp MusD-Dac1J inserted at the Fgf8 locus (mm10, chr19:45,100,000–45,900,000). The full-length element contains retroviral (gag, pro, pol) and non-retroviral sequences flanked by 5′LTR and 3′LTR. RepeatMasker names are indicated in green. b, The mouse Fbxw4–Fgf8 locus is shown in wild-type mice (top) or with the intergenic MusD-Dac1J insertion in Dac1J/Dac1J C57BL/6 (middle) or Dac1J/Dac1J 129s2/Sv (bottom). The number and localization of the CpG measured in d are indicated in red. c, Skeletal analysis of the forelimbs and hindlimbs of E18.5 wild-type (top), Dac1J/Dac1J C57BL/6 (middle) or 129s2/Sv (bottom) mice, stained with alcian blue (cartilage) and alizarin red (bone). Scale bars, 1 mm. d, DNA methylation status of five CpGs upstream of the insertion, 19 CpGs in the 5′LTR (promoter) of Dac1J and eight CpGs downstream of the insertion in wild-type (C57BL/6 and 129s2/Sv, top), Dac1J/Dac1J C57BL/6 (middle) or 129s2/Sv (bottom) mice measured by bisulfite cloning and sequencing from E11.5 limbs. White circles, unmethylated CpGs; black circles, methylated CpGs. e, Schematic representation of the CRISPR–Cas9 Dac1J deletion in the Dac1J/Dac1J (129s2/Sv) line. f, Skeletal analysis of E18.5 Dac1J Δ/Δ (129s2/Sv) forelimbs and hindlimbs showing complete rescue. Scale bars, 1 mm. n = 11 out of 11 E18.5 showed a similar phenotype. g, CpG DNA methylation status in Dac1J Δ/Δ (129s2/Sv) E11.5 limbs as in d.

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