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

Autor: Takayuki Suzuki, Chizuko Nishida, Aki Koike, Mitsuo Nunome, Yoichi Matsuda, Kenji Ichiyanagi, Manabu Koike, Keiji Kinoshita, Takeo Uemura
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
Medicine (miscellaneous)
Apoptosis
Chick Embryo
medicine.disease_cause
0302 clinical medicine
lcsh:QH301-705.5
Cells
Cultured
Chromosome 7 (human)
Mutation
biology
Homozygote
Gene Expression Regulation
Developmental
Bone development
Embryo
Cell Differentiation
DNA-Binding Proteins
Phenotype
embryonic structures
General Agricultural and Biological Sciences
Chondrodystrophy
Heterozygote
Indian hedgehog
animal structures
DNA repair
Embryonic Development
Development
General Biochemistry
Genetics and Molecular Biology
Bone and Bones
Article
03 medical and health sciences
medicine
Animals
Genetic Predisposition to Disease
Hedgehog Proteins
Gene
Poultry Diseases
Cell Proliferation
Animal breeding
Bone Diseases
Developmental
Heterozygote advantage
biology.organism_classification
medicine.disease
Molecular biology
030104 developmental biology
DNA Repair Enzymes
lcsh:Biology (General)
030217 neurology & neurosurgery
Gene Deletion
Zdroj: Communications Biology, Vol 3, Iss 1, Pp 1-11 (2020)
Communications Biology
ISSN: 2399-3642
DOI: 10.1038/s42003-020-0870-z
Popis: 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.
Kinoshita et al find that the classical Creeper (Cp) phenotype in chicken is caused by a deletion containing not only the gene encoding Indian hedgehog, previously implicated in the Cp trait, but also the NHEJ1 gene encoding a DNA repair factor. They show that early death in Cp/Cp chicken is caused by impaired DNA repair and abnormalities of the vascular and nervous systems.
Databáze: OpenAIRE
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