Generation of a heterozygous COL1A1 (c.3969_3970insT) osteogenesis imperfecta mutation human iPSC line, MCRIi001-A-1, using CRISPR/Cas9 editing

Hani Hosseini Far; Yudha Nur Patria; Ali Motazedian; Andrew G Elefanty; Edouard G Stanley; Shireen R Lamandé; John F Bateman

doi:10.1016/j.scr.2019.101449

Generation of a heterozygous COL1A1 (c.3969_3970insT) osteogenesis imperfecta mutation human iPSC line, MCRIi001-A-1, using CRISPR/Cas9 editing

Stem Cell Res. 2019 May:37:101449. doi: 10.1016/j.scr.2019.101449. Epub 2019 Apr 23.

Authors

Hani Hosseini Far¹, Yudha Nur Patria¹, Ali Motazedian², Andrew G Elefanty³, Edouard G Stanley³, Shireen R Lamandé¹, John F Bateman⁴

Affiliations

¹ Murdoch Children's Research Institute, University of Melbourne, Australia; Department of Paediatrics, University of Melbourne, Australia.
² Murdoch Children's Research Institute, University of Melbourne, Australia.
³ Murdoch Children's Research Institute, University of Melbourne, Australia; Department of Paediatrics, University of Melbourne, Australia; Department of Anatomy and Developmental Biology, Monash University, Australia.
⁴ Murdoch Children's Research Institute, University of Melbourne, Australia; Department of Biochemistry and Molecular Biology, University of Melbourne, Australia. Electronic address: john.bateman@mcri.edu.au.

PMID: 31075690
DOI: 10.1016/j.scr.2019.101449

Abstract

To develop a disease model for the human 'brittle bone' disease, osteogenesis imperfecta, we have used gene editing to produce a facsimile of the patient heterozygous COL1A1 mutation in an established control iPSC line. The gene-edited line had a normal karyotype, expressed pluripotency markers and differentiated into cells representative of the three embryonic germ layers. This iPSC line and the isogenic parental iPSC line will be of use in exploring osteogenesis imperfecta disease mechanisms and therapeutic approaches in vitro.

Publication types

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

MeSH terms

CRISPR-Cas Systems*
Cell Differentiation
Cells, Cultured
Cellular Reprogramming
Collagen Type I / genetics*
Collagen Type I, alpha 1 Chain
Gene Editing*
Heterozygote
Humans
Induced Pluripotent Stem Cells / metabolism
Induced Pluripotent Stem Cells / pathology*
Leukocytes, Mononuclear / metabolism
Leukocytes, Mononuclear / pathology*
Male
Middle Aged
Mutation*
Osteogenesis Imperfecta / genetics*
Osteogenesis Imperfecta / pathology
Phenotype

Substances

Collagen Type I
Collagen Type I, alpha 1 Chain