A family knockout of all four Drosophila metallothioneins reveals a central role in copper homeostasis and detoxification

Molecular and Cellular Biology
Dieter EgliWalter Schaffner

Abstract

Metallothioneins are ubiquitous, small, cysteine-rich proteins with the ability to bind heavy metals. In spite of their biochemical characterization, their in vivo function remains elusive. Here, we report the generation of a metallothionein gene family knockout in Drosophila melanogaster by targeted disruption of all four genes (MtnA to -D). These flies are viable if raised in standard laboratory food. During development, however, they are highly sensitive to copper, cadmium, and (to a lesser extent) zinc load. Metallothionein expression is particularly important for male viability; while copper load during development affects males and females equally, adult males lacking metallothioneins display a severely reduced life span, possibly due to copper-mediated oxidative stress. Using various reporter gene constructs, we find that different metallothioneins are expressed with virtually the same tissue specificity in larvae, notably in the intestinal tract at sites of metal accumulation, including the midgut's "copper cells." The same expression pattern is observed with a synthetic minipromoter consisting only of four tandem metal response elements. From these and other experiments, we conclude that tissue specificity of metalloth...Continue Reading

References

Mar 1, 1992·The Journal of Nutrition·E D Harris
Jan 1, 1991·Methods in Enzymology·J H Kägi
May 15, 1989·The Biochemical Journal·M BeltraminiK Lerch
Apr 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·J P PhillipsA J Hilliker
May 1, 1989·Toxicology Letters·J Abel, N de Ruiter
Jan 1, 1987·Experientia. Supplementum·D M Durnam, R D Palmiter
May 1, 1971·Proceedings of the National Academy of Sciences of the United States of America·J M McCordI Fridovich
Oct 1, 1995·Biometals : an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine·M DurliatM Wegnez
Sep 1, 1994·Environmental Health Perspectives·P F Predki, B Sarkar
Jan 18, 1994·Proceedings of the National Academy of Sciences of the United States of America·B A MastersR D Palmiter
Sep 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·K T TamaiD J Thiele
Sep 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·A E Michalska, K H Choo
Oct 15, 1996·Archives of Biochemistry and Biophysics·A R QuesadaD H Petering
May 19, 1998·Trends in Biochemical Sciences·C Askwith, J Kaplan
May 20, 1998·The American Journal of Clinical Nutrition·S S Percival
Jun 11, 1999·Journal of Cellular Physiology·M MurataS Koizumi
Jul 30, 1999·Biochemical and Biophysical Research Communications·J CamakarisJ F Mercer
Dec 10, 1999·Nature·A J BerghammerE A Wimmer
Dec 22, 1999·Proceedings of the Society for Experimental Biology and Medicine·Y J Kang
Jan 19, 2000·Trends in Biochemical Sciences·M D HarrisonC T Dameron
Sep 28, 2000·Biochemical and Biophysical Research Communications·M HayashiT Okui
Jan 11, 2001·Development Genes and Evolution·C HornE A Wimmer
Feb 24, 2001·Industrial Health·H Yamada, S Koizumi
Mar 19, 2002·Journal of Inorganic Biochemistry·Núria Romero-Isart, Milan Vasák
Mar 29, 2002·Microscopy Research and Technique·Christiane Ballan-Dufrançais
Jun 1, 2002·Current Opinion in Chemical Biology·Sergi Puig, Dennis J Thiele
Jun 25, 2002·Genes & Development·Yikang S RongKent G Golic
Jul 24, 2002·Biochemistry·Andreas SimonsGerd Multhaup
Dec 31, 2002·FEBS Letters·J DomenechS Atrian

❮ Previous
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Citations

Oct 14, 2008·Genes & Nutrition·Maria Laura Scarino
Aug 28, 2013·Proceedings of the National Academy of Sciences of the United States of America·Guiran XiaoBing Zhou
Mar 16, 2013·International Journal of Phytoremediation·Nasser AmerStefano Dumontet
Mar 9, 2011·Molecular and Cellular Biology·Nidhi SainiWalter Schaffner
Mar 16, 2007·PloS One·Silvia DíazJuan C Gutiérrez
Oct 10, 2014·Biometals : an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine·Polychronis RempoulakisFanis Missirlis
Apr 6, 2011·Biometals : an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine·Haiqing HuaWalter Schaffner
Jul 7, 2012·Cellular and Molecular Life Sciences : CMLS·Yasmina MansoJuan Hidalgo
Aug 27, 2011·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Lilit AtanesyanWalter Schaffner
Feb 7, 2016·Journal of Hazardous Materials·Jaya Mary JacobRaj Mohan Balakrishnan
Dec 6, 2011·The International Journal of Biochemistry & Cell Biology·Viola GüntherWalter Schaffner
Jun 28, 2011·Ecotoxicology and Environmental Safety·Nathalie ArnalCarlos A Marra
Feb 3, 2016·Journal of Alzheimer's Disease : JAD·Yasmina MansoJuan Hidalgo
Mar 31, 2007·Trends in Genetics : TIG·Louise V O'KeefeRobert I Richards
Jan 9, 2007·Comparative Biochemistry and Physiology. Toxicology & Pharmacology : CBP·Gianfranco SantovitoEster Piccinni
May 24, 2006·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Dieter EgliSílvia Atrian
Oct 31, 2006·Insect Molecular Biology·M Corona, G E Robinson
Jun 19, 2012·Basic & Clinical Pharmacology & Toxicology·Yuhui HaoYongping Su
Jun 14, 2014·Physiological Entomology·Mario H Perez, Fernando G Noriega
Jun 21, 2006·Biochimica Et Biophysica Acta·Kuppusamy Balamurugan, Walter Schaffner
May 4, 2016·Archives of Biochemistry and Biophysics·Guiran Xiao, Bing Zhou
Sep 11, 2013·Annual Review of Genetics·Bruno Lemaitre, Irene Miguel-Aliaga

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