Targeted disruption of CRE-binding factor TREE5 gene leads to cellular necrosis in cardiac myocytes at the embryonic stage

TREB5 (hXBP-1) is a basic region leucine zipper protein which binds to a CR E-like element in both human T-cell leukemia virus type 1 and MHC class II genes. To study the function(s) of TREB5 in normal development, we have gen erated TREB5 deficient mice by gene targeting. Heterozygous mutant mice hav e not exhibited any obvious abnormalities; however, homozygous mutant embry os die between embryonic days 10.5 and 14.5. The major defect responsible f or lethality is cellular necrosis of cardiac myocytes located at the atrium and the truncus arteriosus with its following ventricle. Necrotic alterati on was not observed in either the endocardial cushion or the conotruncal ri dge. These results indicate that TREB5 plays an essential role in maintenan ce and/or growth of cardiac myocytes during cardiogenesis. (C) 1999 Academi c Press.