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Related Experiment Videos

Gene expression analysis of the acute phase response using a canine microarray.

M A Higgins1, B R Berridge, B J Mills

  • 1Department of Lead Optimization Toxicology, Lilly Research Laboratories, Eli Lilly and Company, Greenfield, IN 46140, USA.

Toxicological Sciences : an Official Journal of the Society of Toxicology
|May 30, 2003
PubMed
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A new canine microarray tool aids pharmaceutical safety assessment by monitoring gene expression in dogs. This genomic tool identifies biomarkers and enhances understanding of inflammatory responses in preclinical drug safety studies.

Area of Science:

  • Genomics and Bioinformatics
  • Preclinical Drug Safety Assessment
  • Comparative Medicine

Background:

  • Pharmaceutical safety evaluation relies on preclinical models, primarily dogs and rats.
  • Understanding adverse effects in preclinical species is crucial for improved safety assessment.
  • Limited tools exist for mechanistic studies and biomarker identification in canine models.

Purpose of the Study:

  • To develop a custom Affymetrix-based oligonucleotide microarray for monitoring thousands of canine genes.
  • To enhance cross-species hybridization by utilizing homologous coding regions for human-derived probes.
  • To assess the utility of the canine array in detecting differential gene expression and identifying biomarkers.

Main Methods:

  • Development of a custom canine microarray with 22,774 probe sets (13,729 canine, 9,045 human-derived).

Related Experiment Videos

  • Modification of human-derived probes to target homologous coding regions for improved hybridization.
  • Assessment of basal gene expression in dog liver and evaluation of differential gene expression during an acute phase response induced by lipopolysaccharide (LPS).

    • Main Results:

    • The canine array successfully detected basal canine gene expression and identified additional liver transcripts using human-derived probes.
    • LPS challenge induced an acute inflammatory response, with marked induction of cytokine and acute phase protein transcripts at 4 hours.
    • Significant changes in transcripts related to glucose homeostasis, biotransformation, and extracellular matrix remodeling were observed at 24 hours post-LPS.
    • The array identified potential biomarkers of hepatic inflammation, showing strong correlations with clinical chemistry parameters like serum amyloid A (SAA), albumin, and alkaline phosphatase (ALP).

    Conclusions:

    • The developed canine genomic tool effectively monitors gene expression and reveals novel aspects of the acute phase response in dogs.
    • This microarray provides a valuable resource for mechanistic studies and biomarker discovery in canine preclinical safety assessments.
    • The findings contribute to a better understanding of inflammatory processes and improve the predictive value of preclinical safety evaluations.