Human pluripotent stem cells as disease models for trinucleotide instability in myotonic dystrophy type I

Project Details

Description

Myotonic dystrophy type 1 (DM1) is an inherited disease; patients suffer from muscle weakness, cardiac problems, cataracts, diabetes and male infertility. Newborns with congenital DM1 (CDM1) show severe generalised weakness, and a high mortality. It was found that the dystrophia myotonica protein kinase (DMPK) gene contains a repeat of three base pairs (CAG.CTG), which is expanded beyond 50-80 repeats in patients but is always smaller than 50 repeats in normal individuals. In CDM1, the number of repeats usually exceeds 1000 units.
As the repeat expansion is transmitted to the next generation, it becomes even larger and causes a more severe disease, a concept called anticipation.
The expansion from mother to child is often very large and causes CDM1 in the child. It is also known that the expansion enlarges with age and that this may cause the clinical disease progression. Extensive studies on patient samples, in vitro models, yeast and mouse models, have pointed to different mechanisms of this instability.
However, several authors have cautioned that their models may not be adequate, and that models closer to the situation in human patients are desirable. By using human pluripotent stem cells, such as human embryonic stem cells and induced pluripotent stem cells, and their differentiated derivatives that carry the DM1 mutation naturally, we aim to unravel the different pathways of repeat instability in a human model and with greater relevance for DM1 patients.
AcronymFWOAL777
StatusFinished
Effective start/end date1/01/1531/12/18

Flemish discipline codes

  • Cytology

Keywords

  • biomedical sciences