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Metal-responsive transcription factor-1 (MTF-1) is essential for embryonic liver development and heavy metal detoxification in the adult liver

Wang, Ying and Wimmer, Ursula and Lichtlen, Peter and Inderbitzin, Daniel and Stieger, Bruno and Meier, Peter J. and Hunziker, Lukas and Stallmach, Thomas and Forrer, Rhea and Rülicke, Thomas and Georgiev, Oleg and Schaffner, Walter. (2004) Metal-responsive transcription factor-1 (MTF-1) is essential for embryonic liver development and heavy metal detoxification in the adult liver. The FASEB Journal, Vol. 18, H. 10. S. 1071-1079.

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Official URL: http://edoc.unibas.ch/dok/A5261603

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Abstract

Metal-responsive transcription factor-1 (MTF-1) activates the transcription of metallothionein genes and other target genes in response to heavy metal load and other stresses such as hypoxia and oxidative stress. It also has an essential function during embryogenesis: targeted disruption of Mtf1 in the mouse results in lethal liver degeneration on day 14 of gestation. Here we studied Mtf1 knockout mice at embryonic and adult stages, the latter by means of conditional knockout. Hepatocytes from Mtf1 null mutant and wild-type embryos were taken into culture on day 12.5 of gestation. Both initially appeared normal, but mutant cells were lost within a few days. Furthermore, Mtf1 null hepatocytes were poorly, if at all, rescued by cocultivation with wild-type rat embryo hepatocytes, indicating a cell-autonomous defect. When the Mtf1 gene was excised by Cre recombinase after birth in liver and bone marrow and to a lesser extent in other organs, mice were viable under non-stress conditions but highly susceptible to cadmium toxicity, in support of a role of MTF-1 in coping with heavy metal stress. An additional MTF-1 function was revealed upon analysis of the hematopoietic system in conditional knockout mice where leukocytes, especially lymphocytes, were found to be severely underrepresented. Together, these findings point to a critical role of MTF-1 in embryonic liver formation, heavy metal toxicity, and hematopoiesis.
Faculties and Departments:11 Rektorat und Verwaltung > Vizerektorat Forschung
UniBasel Contributors:Meier-Abt, Peter J.
Item Type:Article, refereed
Bibsysno:Link to catalogue
Publisher:FASEB
ISSN:0892-6638
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:22 Mar 2012 14:23
Deposited On:22 Mar 2012 13:32

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