Cardiac-specific expression of calcineurin reverses embryonic lethality in calreticulin-deficient mouse

Lei Guo, Kimitoshi Nakamura, Jeffery Lynch, Michal Opas, Eric N. Olson, Luis B. Agellon, Marek Michalak

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Abstract

Calreticulin is an endoplasmic reticulum resident Ca2+-binding chaperone. The importance of the protein is illustrated by embryonic lethality because of impaired cardiac development in calreticulin-deficient mice. The molecular details underlying this phenotype are not understood. In this study, we show that overexpression of activated calcineurin reverses the defect in cardiac development observed in calreticulin-deficient mice and rescues them from embryonic lethality. The surviving mice show no defect in cardiac development but exhibited growth retardation, hypoglycemia, increased levels of serum triacylglycerols, and cholesterol. Reversal of embryonic lethality because of calreticulin deficiency by activated calcineurin underscores the impact of the calreticulin-calcineurin functions on the Ca2+-dependent signaling cascade during early cardiac development. These findings show that calreticulin and calcineurin play fundamental roles in Ca2+-dependent pathways essential for normal cardiac development and explain the molecular basis for the rescue of calreticulin-deficient phenotype.

Original languageEnglish (US)
Pages (from-to)50776-50779
Number of pages4
JournalJournal of Biological Chemistry
Volume277
Issue number52
DOIs
Publication statusPublished - Dec 27 2002

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ASJC Scopus subject areas

  • Biochemistry

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