A Transgenic Mouse Model for Monitoring Endoplasmic Reticulum Stress

Nat Med. 2004 Jan;10(1):98-102. doi: 10.1038/nm970. Epub 2003 Dec 14.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • DNA-Binding Proteins / genetics
  • Endoplasmic Reticulum / physiology*
  • Mice
  • Mice, Transgenic
  • Models, Animal
  • RNA Splicing
  • RNA, Messenger / metabolism
  • Recombinant Fusion Proteins / genetics
  • Regulatory Factor X Transcription Factors
  • Stress, Physiological / physiopathology*
  • Transcription Factors / genetics
  • X-Box Binding Protein 1

Substances

  • DNA-Binding Proteins
  • RNA, Messenger
  • Recombinant Fusion Proteins
  • Regulatory Factor X Transcription Factors
  • Transcription Factors
  • X-Box Binding Protein 1
  • XBP-1 venus fusion protein
  • Xbp1 protein, mouse