Wolfram Syndrome iPS Cells: The First Human Cell Model of Endoplasmic Reticulum Disease

  1. Fumihiko Urano
  1. Department of Medicine, Division of Endocrinology, Metabolism, and Lipid Research, Washington University School of Medicine, St. Louis, MO; and Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO
  1. Corresponding author: Fumihiko Urano, urano{at}dom.wustl.edu.

Wolfram syndrome is a rare autosomal recessive genetic disorder with clinical signs apparent in early childhood. This condition is characterized by childhood-onset diabetes, optic nerve atrophy, deafness, diabetes insipidus, and neurodegeneration, and it results in death in middle adulthood (13). Genetic and experimental evidence strongly suggest that endoplasmic reticulum (ER) dysfunction is a critical pathogenic component of Wolfram syndrome (4,5). However, there is a lack of complete understanding of the pathways and biomarkers involved in the disease process due to the limitations of animal models that do not accurately reflect human patients. As a result, despite the underlying importance of ER dysfunction in Wolfram syndrome, there are currently no therapies that target the ER, a deficiency that points to the urgent need to develop a human cell model of this condition. In this issue, Shang et al. (6) report that this has been successfully accomplished.

ER is a membrane network within the cytoplasm of cells that is involved in protein synthesis, calcium storage, redox regulation, steroid synthesis, and cell death. Recent clinical and genetic evidence indicate that acquired or inherited ER dysfunction can cause rare genetic diseases such as Wolfram syndrome, as well as many …

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