Microarray analysis of murine limb bud ectoderm and mesoderm after exposure to cadmium or acetazolamide
Article first published online: 9 MAR 2009
Copyright © 2009 Wiley-Liss, Inc.
Birth Defects Research Part A: Clinical and Molecular Teratology
Volume 85, Issue 7, pages 588–598, July 2009
How to Cite
Schreiner, C. M., Bell, S. M. and Scott, W. J. (2009), Microarray analysis of murine limb bud ectoderm and mesoderm after exposure to cadmium or acetazolamide. Birth Defects Research Part A: Clinical and Molecular Teratology, 85: 588–598. doi: 10.1002/bdra.20577
- Issue published online: 8 JUL 2009
- Article first published online: 9 MAR 2009
- Manuscript Accepted: 22 JAN 2009
- Manuscript Revised: 13 JAN 2009
- Manuscript Received: 22 JAN 2008
- NIH. Grant Number: R21 ES11750
- limb buds
BACKGROUND: A variety of drugs, environmental chemicals, and physical agents induce a common limb malformation in the offspring of pregnant mice exposed on day 9 of gestation. This malformation, postaxial, right-sided forelimb ectrodactyly, is thought to arise via an alteration of hedgehog signaling. METHODS: We have studied two of these teratogens, acetazolamide and cadmium, using the technique of microarray analysis of limb bud ectoderm and mesoderm to search for changes in gene expression that could indicate a common pathway to postaxial limb reduction. RESULTS: Results indicated a generalized up-regulation of gene expression after exposure to acetazolamide but a generalized down-regulation due to cadmium exposure. An intriguing observation was a cadmium-induced reduction of Mt1 and Mt2 expression in the limb bud mesoderm indicating a lowering of embryonic zinc. CONCLUSIONS: We propose that these two teratogens and others (valproic acid and ethanol) lower sonic hedgehog signaling by perturbation of zinc function in the sonic hedgehog protein. Birth Defects Research (Part A), 2009. © 2009 Wiley-Liss, Inc.