The Creeper (Cp) chicken is characterized by chondrodystrophy in Cp/+ heterozygotes and embryonic lethality in Cp/Cp homozygotes. However, the genes underlying the phenotypes have not been fully known. Here, we show that a 25 kb deletion on chromosome 7, which contains the Indian hedgehog (IHH) and non-homologous end-joining factor 1 (NHEJ1) genes, is responsible for the Cp trait in Japanese bantam chickens. IHH is essential for chondrocyte maturation and is downregulated in the Cp/+ embryos and completely lost in the Cp/Cp embryos. This indicates that chondrodystrophy is caused by the loss of IHH and that chondrocyte maturation is delayed in Cp/+ heterozygotes. The Cp/Cp homozygotes exhibit impaired DNA double-strand break (DSB) repair due to the loss of NHEJ1, resulting in DSB accumulation in the vascular and nervous systems, which leads to apoptosis and early embryonic death.

Creeper ( Cp ) 鸡的特征是Cp /+ 杂合子的软骨营养不良和Cp / Cp纯合子的胚胎致死率。然而，表型背后的基因尚未完全清楚。在这里，我们显示 7 号染色体上的 25 kb 缺失，其中包含印度刺猬 ( IHH ) 和非同源末端连接因子 1 ( NHEJ1 ) 基因，是造成日本矮脚鸡Cp性状的原因。IHH为软骨细胞成熟是必需的，并在被下调的Cp / +胚胎和完全失去了在的Cp /的Cp胚胎。这表明软骨营养不良是由IHH的缺失引起的，并且Cp / +杂合子中软骨细胞成熟延迟。所述的Cp /的Cp纯合子表现出受损的DNA双链断裂（DSB）修复由于损失NHEJ1，导致在血管和神经系统，这导致细胞凋亡和早期胚胎死亡DSB积累。