Doctoral defence: Marilin Ivask “Transcriptomic and metabolic changes in the WFS1-deficient mouse model”

On 29 November at 15:00 Marilin Ivask will defend her doctoral thesis “Transcriptomic and metabolic changes in the WFS1-deficient mouse model”.

Professor Sulev Kõks, University of Tartu
Professor Emeritus Atso Ilari Raasmaja, University on Helsinki (Finland)

Associate Professor Kirsi A. Virtanen, University of Turku (Finland)

Wolfram syndrome (WFS) is a rare inherited disease characterized by juvenile-onset insulin-dependent diabetes, optic nerve atrophy, diabetes insipidus, deafness and several neurological abnormalities. The diseases caused by mutations in the WFS1 gene. WFS1 plays a number of roles in the cell, participating in membrane transport, protein processing, and the cellular response to accumulation of unfolded proteins in the endoplasmic reticulum (ER). There is growing evidence that abnormalities in ER homeostasis and chronic ER stress are important in the development of many diseases, such as neurodegenerative diseases and diabetes. WFS1 levels in case of ER stress usually increase, and the absence of WFS1 contributes to chronic ER stress and cell death. This in turn causes the symptoms of the disease to develop and worsen.

The aim of this study was to identify possible transcriptomic and metabolic changes due to WFS1 deficiency in a WFS mouse model that contribute to the development of WFS symptoms. WFS1 deficiency causes transcriptomic changes in the hypothalamus, hippocampus, and pancreatic islets of Langerhans, which contribute to the development and exacerbation of a variety of endocrine, neurodegenerative, and behavioral symptoms associated with the disease. WFS1 deficiency reduces the number of pancreatic islets and impairs insulin secretion. WFS1 deficiency also causes metabolic abnormalities, because Wfs1 mutant mice weigh significantly less and have a shorter lifespan than their normal littermates. A high fat diet causes a variety of metabolic changes in mice with a single copy of the active Wfs1 gene, such as weight gain, changes in insulin secretion, and changes in ER stress-related gene expression. However, the heterozygosity of Wfs1 causes variation in the expression patterns of both metabolic complications and ER stress-mediating genes associated with the development of adverse metabolic disorders and symptoms related to Wolfram syndrome.

The defence will be also held in MS Teams.