Biochem. Soc. Trans (2005) 33, 1534-1536 - S.A. Duncan

Medline/PubMed Citation | Related Articles in PubMed | Download to Citation Manager

Biochemical Society Transactions (2005) 33, (1534–1536) (Printed in Great Britain)

PDF

Legacy HTML

Send to a friend

Add a comment

Focus Topics at BioScience2005

Generation of embryos directly from embryonic stem cells by tetraploid embryo complementation reveals a role for GATA factors in organogenesis

S.A. Duncan¹

Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, U.S.A.

Key words: Cre/loxP, embryonic stem (ES) cells, extra-embryonic endoderm, gastrulation, GATA factor, organogenesis.

Abbreviations used: E 10.5, embryonic day 10.5 (etc.); ES cells, embryonic stem cells; floxed, flanked by loxP; HNF4a, hepatocyte nuclear factor 4a.

Gene targeting in ES (embryonic stem) cells has been used extensively to study the role of proteins during embryonic development. In the traditional procedure, this requires the generation of chimaeric mice by introducing ES cells into blastocysts and allowing them to develop to term. Once chimaeric mice are produced, they are bred into a recipient mouse strain to establish germline transmission of the allele of interest. Although this approach has been used very successfully, the breeding cycles involved are time consuming. In addition, genes that are essential for organogenesis often have roles in the formation of extra-embryonic tissues that are essential for early stages of post-implantation development. For example, mice lacking the GATA transcription factors, GATA4 or GATA6, arrest during gastrulation due to an essential role for these factors in differentiation of extra-embryonic endoderm. This lethality has frustrated the study of these factors during the development of organs such as the liver and heart. Extraembryonic defects can, however, be circumvented by generating clonal mouse embryos directly from ES cells by tetraploid complementation. Here, we describe the usefulness and efficacy of this approach using GATA factors as an example.