IRE1α disruption causes histological abnormality of exocrine tissues, increase of blood glucose level, and decrease of serum immunoglobulin level

Accumulation of unfolded proteins in the endoplasmic reticulum (ER) causes ER stress. As a cellular adaptive response to ER stress, unfolded protein response (UPR) activates molecules for the quality control of ER proteins. One enzyme that plays an important role in UPR is Inositol Requiring Enzyme-...

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Bibliographic Details
Published in:PloS one 2010-09, Vol.5 (9), p.e13052-e13052
Main Authors: Iwawaki, Takao, Akai, Ryoko, Kohno, Kenji
Format: Article
Language:English
Subjects:
Animal tissues
Animals
Biochemistry/Protein Folding
Biosynthesis
Blood Glucose
Cell Biology/Cellular Death and Stress Responses
Cell differentiation
Diabetes
Diabetes and Endocrinology
Disruption
Endoplasmic reticulum
Endoribonucleases - deficiency
Endoribonucleases - genetics
Enzymes
Exocrine glands
Female
Gene Silencing
Glucose
Hyperglycemia
Immunoglobulins
Immunoglobulins - blood
Inflammatory bowel disease
Inositol
Insulin
Kinases
Lipogenesis
Liver
Liver diseases
Machinery and equipment
Male
Mammals
Mice
Mice, Inbred C57BL
Mice, Knockout
mRNA
Organs
Pancreas
Pancreas, Exocrine - abnormalities
Pancreas, Exocrine - metabolism
Plasma cells
Protein folding
Protein-Serine-Threonine Kinases - deficiency
Protein-Serine-Threonine Kinases - genetics
Proteins
Quality control
Rodents
Salivary Glands - abnormalities
Salivary Glands - metabolism
Signal transduction
Splicing
Stress
Stresses
Transcription factors
Yeast
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Summary:Accumulation of unfolded proteins in the endoplasmic reticulum (ER) causes ER stress. As a cellular adaptive response to ER stress, unfolded protein response (UPR) activates molecules for the quality control of ER proteins. One enzyme that plays an important role in UPR is Inositol Requiring Enzyme-1 (IRE1), which is highly conserved from yeast to humans. In particular, mammalian IRE1α activates X-box-binding protein 1 (XBP1) by unconventional splicing of XBP1 mRNA during ER stress. From analysis of knockout mice, both IRE1α and XBP1 have been shown to be essential for development and that XBP1 is necessary for the secretory machinery of exocrine glands, plasma cell differentiation, and hepatic lipogenesis. However, the essentiality of IRE1α in specific organs and tissues remains incompletely understood. Here, we analyzed the phenotype of IRE1α conditional knockout mice and found that IRE1α-deficient mice exhibit mild hypoinsulinemia, hyperglycemia, and a low-weight trend. Moreover, IRE1α disruption causes histological abnormality of the pancreatic acinar and salivary serous tissues and decrease of serum level of immunoglobulin produced in the plasma cells, but not dysfunction of liver. Comparison of this report with previous reports regarding XBP1 conditional knockout mice might provide some clues for the discovery of the novel functions of IRE1α and XBP1.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0013052