Combined deletions of IHH and NHEJ1 cause chondrodystrophy and embryonic lethality in the Creeper chicken

Keiji Kinoshita; Takayuki Suzuki; Manabu Koike; Chizuko Nishida; Aki Koike; Mitsuo Nunome; Takeo Uemura; Kenji Ichiyanagi; Yoichi Matsuda

doi:10.1038/s42003-020-0870-z

Combined deletions of IHH and NHEJ1 cause chondrodystrophy and embryonic lethality in the Creeper chicken

Commun Biol. 2020 Mar 25;3(1):144. doi: 10.1038/s42003-020-0870-z.

Authors

Keiji Kinoshita^#^{1

2}, Takayuki Suzuki^#^{1

3}, Manabu Koike^#⁴, Chizuko Nishida⁵, Aki Koike⁴, Mitsuo Nunome¹, Takeo Uemura¹, Kenji Ichiyanagi⁶, Yoichi Matsuda^{7

8}

Affiliations

¹ Avian Bioscience Research Center, Graduate School of Bioagricultural Sciences, Nagoya University, Chikusa-ku, Nagoya, Aichi, 464-8601, Japan.
² State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, Yunnan Agricultural University, Kunming, 650201, China.
³ Laboratory of Avian Bioscience, Department of Animal Sciences, Graduate School of Bioagricultural Sciences, Nagoya University, Chikusa-ku, Nagoya, Aichi, 464-8601, Japan.
⁴ National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Inage-ku, Chiba, 263-8555, Japan.
⁵ Department of Natural History Sciences, Faculty of Science, Hokkaido University, Kita-ku, Sapporo, Hokkaido, 060-0808, Japan.
⁶ Laboratory of Genome and Epigenome Dynamics, Department of Animal Sciences, Graduate School of Bioagricultural Sciences, Nagoya University, Chikusa-ku, Nagoya, Aichi, 464-8601, Japan.
⁷ Avian Bioscience Research Center, Graduate School of Bioagricultural Sciences, Nagoya University, Chikusa-ku, Nagoya, Aichi, 464-8601, Japan. [email protected].
⁸ Laboratory of Avian Bioscience, Department of Animal Sciences, Graduate School of Bioagricultural Sciences, Nagoya University, Chikusa-ku, Nagoya, Aichi, 464-8601, Japan. [email protected].

^# Contributed equally.

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Apoptosis
Bone Diseases, Developmental / embryology
Bone Diseases, Developmental / genetics
Bone Diseases, Developmental / metabolism
Bone Diseases, Developmental / veterinary*
Bone and Bones / embryology*
Bone and Bones / metabolism
Cell Differentiation
Cell Proliferation
Cells, Cultured
Chick Embryo
DNA Repair Enzymes / deficiency
DNA Repair Enzymes / genetics*
DNA-Binding Proteins / deficiency
DNA-Binding Proteins / genetics*
Embryonic Development
Gene Deletion*
Gene Expression Regulation, Developmental
Genetic Predisposition to Disease
Hedgehog Proteins / deficiency
Hedgehog Proteins / genetics*
Heterozygote
Homozygote
Phenotype
Poultry Diseases / embryology
Poultry Diseases / genetics*
Poultry Diseases / metabolism

Substances

DNA-Binding Proteins
Hedgehog Proteins
DNA Repair Enzymes