2020/03/25 by Keiji Kinoshita, Takayuki Suzuki, Manabu Koike +6 · 1 citation
Biochemistry, Genetics and Molecular Biology · #Cancer, Hypoxia, and Metabolism #Epigenetics and DNA Methylation #RNA modifications and cancer
paper · pdf · doi:10.1038/s42003-020-0870-z
openalex publication_date 2020/03/25 · openalex created_date 2020/04/03 · openalex updated_date 2026/07/23
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.