Open AccessEstablishment of maturity‐onset diabetes of the young‐induced pluripotent stem cells from a Japanese patient
Author(s) -
Yabe Shigeharu G,
Iwasaki Naoko,
Yasuda Kazuki,
Hamazaki Tatsuo S,
Konno Masamitsu,
Fukuda Satsuki,
Takeda Fujie,
Kasuga Masato,
Okochi Hitoshi
Publication year - 2015
Publication title -
journal of diabetes investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.089
H-Index - 50
eISSN - 2040-1124
pISSN - 2040-1116
DOI - 10.1111/jdi.12334
Subject(s) - induced pluripotent stem cell , maturity onset diabetes of the young , medicine , diabetes mellitus , mutant , stem cell , endocrinology , microbiology and biotechnology , gene , biology , genetics , embryonic stem cell , type 2 diabetes
Maturity‐onset diabetes of the young ( MODY ) is a heterozygous monogenic diabetes; more than 13 disease genes have been identified. However, the pathogenesis of MODY is not fully understood, because the pancreatic β‐cells of the patients are inaccessable. Therefore, we attempted to establish MODY patient‐derived induced pluripotent stem cells ( MODY ‐ iPS ) cells to investigate the pathogenic mechanism of MODY by inducing pancreatic β‐cells. We established MODY 5‐ iPS cells from a Japanese patient with MODY 5 (R177X), and confirmed that MODY 5‐ iPS cells possessed the characteristics of pluripotent stem cells. In the course of differentiation from MODY 5‐ iPS cells into pancreatic β‐cells, we examined the disease gene, HNF 1B messenger ribonucleic acid. We found that the amount of R177X mutant transcripts was much less than that of wild ones, but they increased after adding cycloheximide to the medium. These results suggest that these R177X mutant messenger ribonucleic acids are disrupted by nonsense‐mediated messenger ribonucleic acid decay in MODY ‐ iPS cells during the developmental stages of pancreatic β‐cells.