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An ENU-induced splice site mutation of mouse Col1a1 causing recessive osteogenesis imperfecta and revealing a novel splicing rescue

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Title: An ENU-induced splice site mutation of mouse Col1a1 causing recessive osteogenesis imperfecta and revealing a novel splicing rescue
Authors: Tabeta, K. Browse this author
Du, X. Browse this author
Arimatsu, K. Browse this author
Yokoji, M. Browse this author
Takahashi, N. Browse this author
Amizuka, N. Browse this author →KAKEN DB
Hasegawa, T. Browse this author →KAKEN DB
Crozat, K. Browse this author
Maekawa, T. Browse this author
Miyauchi, S. Browse this author
Matsuda, Y. Browse this author
Ida, T. Browse this author
Kaku, M. Browse this author
Hoebe, K. Browse this author
Ohnom, K. Browse this author
Yoshie, H. Browse this author
Yamazaki, K. Browse this author
Moresco, EM. Browse this author
Beutler, B. Browse this author
Issue Date: 15-Sep-2017
Publisher: Nature Publishing Group
Journal Title: Scientific reports
Volume: 7
Start Page: 11717
Publisher DOI: 10.1038/s41598-017-10343-9
Abstract: GU-AG consensus sequences are used for intron recognition in the majority of cases of pre-mRNA splicing in eukaryotes. Mutations at splice junctions often cause exon skipping, short deletions, or insertions in the mature mRNA, underlying one common molecular mechanism of genetic diseases. Using N-ethyl-N-nitrosourea, a novel recessive mutation named seal was produced, associated with fragile bones and susceptibility to fractures (spine and limbs). A single nucleotide transversion (T → A) at the second position of intron 36 of the Col1a1 gene, encoding the type I collagen, α1 chain, was responsible for the phenotype. Col1a1 seal mRNA expression occurred at greatly reduced levels compared to the wild-type transcript, resulting in reduced and aberrant collagen fibers in tibiae of seal homozygous mice. Unexpectedly, splicing of Col1a1 seal mRNA followed the normal pattern despite the presence of the donor splice site mutation, likely due to the action of a putative intronic splicing enhancer present in intron 25, which appeared to function redundantly with the splice donor site of intron 36. Seal mice represent a model of human osteogenesis imperfecta, and reveal a previously unknown mechanism for splicing “rescue.”
Type: article
Appears in Collections:歯学院・歯学研究院 (Graduate School of Dental Medicine / Faculty of Dental Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 長谷川 智香

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