Exome sequencing and CRISPR/Cas genome editing identify mutations of ZAK as a cause of limb defects in humans and mice

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Figure 4.
Figure 4.

Limb defects in CRISPR/Cas mice with a deletion of the ZAK SAM domain. (A) At E18.5, one supernumerary hindlimb with normal polarity was connected to an imperfectly duplicated pelvic girdle. The duplicated hindlimb showed a shortened femur, fibula, and tibia and normal-sized digits. (B) A 5-wk-old mouse showed a partial duplication of the right hindlimb and pelvic structures. (C) The foot was completely duplicated (blue) and connected by a common digit V with a distal duplication (red). The fibula and tibia were only partially duplicated. (D) The right femur shaft was split, and the distal and proximal parts (red) were duplicated. The left femur appeared normal (blue). (E) Expression analysis of Zakdel/del homozygous mutant (MT) hindlimbs at E11.5 showed a 60% decrease of Trp63 expression compared with wild-type (WT) hindlimbs. Error bars, SD.

This Article

  1. Genome Res. 26: 183-191

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