Nonredundant roles of the elongation factor MEN in postimplantation development

The MEN/ELL gene was cloned as a fusion partner of the MLL gene in the t(11 ;19)(q23;p13.1) translocation, which is found in adult myeloid leukemia. ME N belongs to a family of RNA polymerase II elongation factors and dysregula ted production of MEN through the MLL promoter could cause malignant transf ormation of myeloid cells. To pursue the physiological role and determine t he requirement of the MEN gene product in mouse development, we generated k nockout mice (MEN-/-) by gene targeting in embryonic stem cells. After inte rcrossing heterozygous mice to generate homozygous mutants, we identified n o homozygotes (MEN-/-) even at E9.5, as well as after birth, by Southern an alysis. Moreover, histological examinations revealed degenerative changes i n nearly one-fourth of E6.5 embryos, which were gradually resorbed by E8.5. Our findings demonstrated that MEN-/- mice are embryonic lethal, and die b efore E6.5 and after implantation. MEN should play a non-redundant role in postimplantation development of mice. (C) 2000 Academic Press.