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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Autores principales: Takao Iwawaki, Ryoko Akai, Kenji Kohno
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Publicado: Public Library of Science (PLoS) 2010
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Acceso en línea:https://doaj.org/article/ae55932060b64a478cb8e10a4dd019a1
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spelling oai:doaj.org-article:ae55932060b64a478cb8e10a4dd019a12021-11-18T06:34:46ZIRE1α disruption causes histological abnormality of exocrine tissues, increase of blood glucose level, and decrease of serum immunoglobulin level.1932-620310.1371/journal.pone.0013052https://doaj.org/article/ae55932060b64a478cb8e10a4dd019a12010-09-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20885949/?tool=EBIhttps://doaj.org/toc/1932-6203Accumulation 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.Takao IwawakiRyoko AkaiKenji KohnoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 9, p e13052 (2010)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Takao Iwawaki
Ryoko Akai
Kenji Kohno
IRE1α disruption causes histological abnormality of exocrine tissues, increase of blood glucose level, and decrease of serum immunoglobulin level.
description 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.
format article
author Takao Iwawaki
Ryoko Akai
Kenji Kohno
author_facet Takao Iwawaki
Ryoko Akai
Kenji Kohno
author_sort Takao Iwawaki
title IRE1α disruption causes histological abnormality of exocrine tissues, increase of blood glucose level, and decrease of serum immunoglobulin level.
title_short IRE1α disruption causes histological abnormality of exocrine tissues, increase of blood glucose level, and decrease of serum immunoglobulin level.
title_full IRE1α disruption causes histological abnormality of exocrine tissues, increase of blood glucose level, and decrease of serum immunoglobulin level.
title_fullStr IRE1α disruption causes histological abnormality of exocrine tissues, increase of blood glucose level, and decrease of serum immunoglobulin level.
title_full_unstemmed IRE1α disruption causes histological abnormality of exocrine tissues, increase of blood glucose level, and decrease of serum immunoglobulin level.
title_sort ire1α disruption causes histological abnormality of exocrine tissues, increase of blood glucose level, and decrease of serum immunoglobulin level.
publisher Public Library of Science (PLoS)
publishDate 2010
url https://doaj.org/article/ae55932060b64a478cb8e10a4dd019a1
work_keys_str_mv AT takaoiwawaki ire1adisruptioncauseshistologicalabnormalityofexocrinetissuesincreaseofbloodglucoselevelanddecreaseofserumimmunoglobulinlevel
AT ryokoakai ire1adisruptioncauseshistologicalabnormalityofexocrinetissuesincreaseofbloodglucoselevelanddecreaseofserumimmunoglobulinlevel
AT kenjikohno ire1adisruptioncauseshistologicalabnormalityofexocrinetissuesincreaseofbloodglucoselevelanddecreaseofserumimmunoglobulinlevel
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