An essential role in liver development for transcription factor XBP-1
- Andreas M. Reimold1,2,
- Amit Etkin1,
- Isabelle Clauss1,
- Andrew Perkins3,
- Daniel S. Friend2,
- John Zhang4,
- Heidi F. Horton5,
- Andrew Scott1,
- Stuart H. Orkin3,
- Michael C. Byrne5,
- Michael J. Grusby1,2, and
- Laurie H. Glimcher1,2,6
- 1Department of Immunology and Infectious Diseases, Harvard School of Public Health, and 2Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115 USA; 3Department of Pediatrics, Harvard Medical School and Howard Hughes Medical Institute, Boston, Massachusetts 02115 USA; 4Division of Rheumatology, Medical University of South Carolina, Charleston, South Carolina 29403 USA; 5Genetics Institute, Cambridge, Massachusetts 02140 USA
Abstract
XBP-1 is a CREB/ATF family transcription factor highly expressed in hepatocellular carcinomas. Here we report that XBP-1 is essential for liver growth. Mice lacking XBP-1 displayed hypoplastic fetal livers, whose reduced hematopoiesis resulted in death from anemia. Nevertheless, XBP-1-deficient hematopoietic progenitors had no cell-autonomous defect in differentiation. Rather, hepatocyte development itself was severely impaired by two measures: diminished growth rate and prominent apoptosis. Specific target genes of XBP-1 in the liver were identified as αFP, which may be a regulator of hepatocyte growth, and three acute phase protein family members. Therefore, XBP-1 is a transcription factor essential for hepatocyte growth.
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Footnotes
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↵6 Corresponding author.
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E-MAIL lglimche{at}hsph.harvard.edu; FAX (617) 432-0084.
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- Received October 12, 1999.
- Accepted December 7, 1999.
- Cold Spring Harbor Laboratory Press
