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Vol. 14, No. 2, pp. 152-157, January 15, 2000
1 Department of Immunology and Infectious Diseases,
Harvard School of Public Health, and 2 Department of Medicine,
Harvard Medical School, Boston, Massachusetts 02115 USA;
3 Department of Pediatrics, Harvard Medical School and Howard
Hughes Medical Institute, Boston, Massachusetts 02115 USA;
4 Division of Rheumatology, Medical University of South
Carolina, Charleston, South Carolina 29403 USA; 5 Genetics
Institute, Cambridge, Massachusetts 02140 USA
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 
FP,
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.
[Key Words: Transcription factors; liver development; acute phase protein; CREB/ATF family; apoptosis; hepatocyte.]
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