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A transgenic mouse model for monitoring endoplasmic reticulum stress

Abstract

Endoplasmic reticulum (ER) stress is caused by the accumulation of unfolded proteins in the ER lumen, and is associated with vascular and neurodegenerative diseases. Although the connection between ER stress and some disease-related proteins has been studied using animal models of these diseases, no in vivo data concerning ER stress are available. Here we report a new method for monitoring ER stress in vivo, based on XBP-1 mRNA splicing by inositol requiring-1 (IRE-1) during ER stress. The stress indicator was constructed by fusing XBP-1 and venus, a variant of green fluorescent protein. During stress, the spliced indicator mRNA is translated into an XBP-1-venus fusion protein, which can be detected by its fluorescence. We used transgenic animals expressing the ER stress indicator to show that it can be used to monitor physiological and pathological ER stress in vivo.

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Figure 1: Schematic of ERAI function.
Figure 2: Characterization of ERAI in vitro.
Figure 3: Characterization of ERAI-transgenic mice.
Figure 4: ER stress in different tissues during tissue maturation.

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Acknowledgements

We thank A. Miyawaki for the venus cDNA and R. Kaufman for the human IRE-1α cDNA. T.I. was a research fellow of the Special Postdoctoral Researchers Program, RIKEN. This work was supported in part by grants from the Japanese Ministry of Education, Science, Sports, Culture, and Technology and by grants from the RIKEN Bioarchitect Research Project.

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Correspondence to Masayuki Miura.

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Iwawaki, T., Akai, R., Kohno, K. et al. A transgenic mouse model for monitoring endoplasmic reticulum stress. Nat Med 10, 98–102 (2004). https://doi.org/10.1038/nm970

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