Microarray analysis identifies keratin loci as sensitive biomarkers for thyroid hormone disruption in the salamander Ambystoma mexicanum

Robert B. Page, James R. Monaghan, Amy K. Samuels, Jeramiah J. Smith, Christopher K. Beachy, S. Randal Voss

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

Ambystomatid salamanders offer several advantages for endocrine disruption research, including genomic and bioinformatics resources, an accessible laboratory model (Ambystoma mexicanum), and natural lineages that are broadly distributed among North American habitats. We used microarray analysis to measure the relative abundance of transcripts isolated from A. mexicanum epidermis (skin) after exogenous application of thyroid hormone (TH). Only one gene had a > 2-fold change in transcript abundance after 2 days of TH treatment. However, hundreds of genes showed significantly different transcript levels at days 12 and 28 in comparison to day 0. A list of 123 TH-responsive genes was identified using statistical, BLAST, and fold level criteria. Cluster analysis identified two groups of genes with similar transcription patterns: up-regulated versus down-regulated. Most notably, several keratins exhibited dramatic (1000 fold) increases or decreases in transcript abundance. Keratin gene expression changes coincided with morphological remodeling of epithelial tissues. This suggests that keratin loci can be developed as sensitive biomarkers to assay temporal disruptions of larval-to-adult gene expression programs. Our study has identified the first collection of loci that are regulated during TH-induced metamorphosis in a salamander, thus setting the stage for future investigations of TH disruption in the Mexican axolotl and other salamanders of the genus Ambystoma.

Original languageEnglish
Pages (from-to)15-27
Number of pages13
JournalComparative Biochemistry and Physiology Part - C: Toxicology and Pharmacology
Volume145
Issue number1
DOIs
StatePublished - Feb 2007

Bibliographical note

Funding Information:
We acknowledge the service of Donna Walls in the UK Microarray Facility. This project was made possible by grant numbers 5R24RR016344, 2P20RR016741, and 2P20RR016481-04 from the National Center for Research Resources, a component of the National Institutes of Health. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of NCRR or NIH. Aspects of this project were also made possible by funding from the U.S. National Science Foundation (IOB-0242833; DBI-0443496) and the Kentucky Spinal Cord and Head Injury Research Trust.

Keywords

  • Ambystoma
  • Endocrine disruption
  • Keratin
  • Metamorphosis
  • Mexican axolotl
  • Microarray
  • RT-PCR
  • Thyroid hormone

ASJC Scopus subject areas

  • Aquatic Science
  • Animal Science and Zoology
  • Biochemistry
  • Physiology
  • Health, Toxicology and Mutagenesis
  • Toxicology
  • Cell Biology

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