Microarray analysis of murine limb bud ectoderm and mesoderm after exposure to cadmium or acetazolamide

Authors

  • Claire M. Schreiner,

    1. Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, and Department of Pediatrics, University of Cincinnati, Cincinnati, Ohio
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  • Sheila M. Bell,

    1. Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, and Department of Pediatrics, University of Cincinnati, Cincinnati, Ohio
    Current affiliation:
    1. Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH
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  • William J. Scott Jr.

    Corresponding author
    1. Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, and Department of Pediatrics, University of Cincinnati, Cincinnati, Ohio
    • Mail Location 7007, Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229
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Abstract

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.

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