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Truncation of the MLL gene in exon 5 by gene targeting leads to early preimplantation lethality of homozygous embryos
Author(s) -
Ayton Paul,
Sneddon Sharon F.,
Palmer Donald B.,
Rosewell Ian R.,
Owen Michael J.,
Young Bryan,
Presley Robert,
Subramanian Vasanta
Publication year - 2001
Publication title -
genesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.093
H-Index - 110
eISSN - 1526-968X
pISSN - 1526-954X
DOI - 10.1002/gene.1066
Subject(s) - biology , genetics , exon , gene , embryo , hox gene , zinc finger , mutant , microbiology and biotechnology , gene expression , transcription factor
Summary: The mixed lineage leukemia gene ( MLL ) was originally identified through its involvement in reciprocal translocations in leukemias. MLL codes for a large multidomain protein and bears homology to the Drosophila developmental control gene trithorax in two small domains in the amino terminal region, the central zinc finger domain and the carboxy SET domain. Like the Drosophila trx, MLL has also been shown to be a positive regulator of Hox gene expression. We have targeted Mll (the murine homologue of MLL ) in exon 5 causing expression of three truncated in‐frame Mll transcripts. These transcripts retain all or some of the AT hook motifs and the DMT domain. This mutant allele causes early in vivo preimplantation lethality of homozygous embryos prior to the 2‐cell stage. Embryos cultured in vitro progress to the 2‐cell stage, but further development is arrested. The heterozygotes exhibit mild skeletal defects as well as defects in some neuroectodermal derivatives. genesis 30:201–212, 2001. © 2001 Wiley‐Liss, Inc.