The use of simultaneous reprogramming and gene correction to generate an osteogenesis imperfecta patient COL1A1 c. 3936 G>T iPSC line and an isogenic control iPSC line

Sara Howden; Hani Hosseini Far; Ali Motazedian; Andrew G Elefanty; Edouard G Stanley; Shireen R Lamandé; John F Bateman

doi:10.1016/j.scr.2019.101453

The use of simultaneous reprogramming and gene correction to generate an osteogenesis imperfecta patient COL1A1 c. 3936 G>T iPSC line and an isogenic control iPSC line

Stem Cell Res. 2019 Jul:38:101453. doi: 10.1016/j.scr.2019.101453. Epub 2019 May 4.

Authors

Sara Howden¹, Hani Hosseini Far², Ali Motazedian¹, Andrew G Elefanty³, Edouard G Stanley³, Shireen R Lamandé², John F Bateman⁴

Affiliations

¹ Murdoch Children's Research Institute, Australia.
² Murdoch Children's Research Institute, Australia; Department of Paediatrics, University of Melbourne, Australia.
³ Murdoch Children's Research Institute, Australia; Department of Paediatrics, University of Melbourne, Australia; Department of Anatomy and Developmental Biology, Monash University, Australia.
⁴ Murdoch Children's Research Institute, Australia; Department of Biochemistry and Molecular Biology, University of Melbourne, Australia. Electronic address: [email protected].

PMID: 31082677
DOI: 10.1016/j.scr.2019.101453

Abstract

To develop a disease model for the human 'brittle bone' disease, osteogenesis imperfecta, we used a simultaneous reprogramming and CRISPR-Cas9 genome editing method to produce an iPSC line with the heterozygous patient mutation (COL1A1 c. 3936 G>T) along with an isogenic gene-corrected control iPSC line. Both IPSC lines had a normal karyotype, expressed pluripotency markers and differentiated into cells representative of the three embryonic germ layers. This osteogenesis imperfecta mutant and isogenic iPSC control line will be of use in exploring disease mechanisms and therapeutic approaches in vitro.

Publication types

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

MeSH terms

Amino Acid Substitution
CRISPR-Cas Systems*
Cell Line
Cellular Reprogramming Techniques*
Collagen Type I* / genetics
Collagen Type I* / metabolism
Collagen Type I, alpha 1 Chain
Humans
Induced Pluripotent Stem Cells* / metabolism
Induced Pluripotent Stem Cells* / pathology
Mutation, Missense*
Osteogenesis Imperfecta* / genetics
Osteogenesis Imperfecta* / metabolism
Osteogenesis Imperfecta* / pathology

Substances

Collagen Type I
Collagen Type I, alpha 1 Chain