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Cell Type-specific Gene Expression Profiling in the Mouse Liver
Published on: September 17, 2019
Hepatic gene expression changes in mice associated with prolonged sublethal microcystin exposure
Shawn P Clark1, Myrtle A Davis, Timothy P Ryan
1Department of Veterinary Pathobiology, Purdue University, Indiana 47907, USA. shawn.clark@bms.com
Toxicologic Pathology
|July 27, 2007
Summary
Chronic exposure to microcystin-LR (MCLR) causes liver damage in mice, affecting cell structure and function. This study used toxicogenomics to identify key molecular pathways altered by sublethal MCLR doses.
Area of Science:
- Toxicology
- Molecular Biology
- Genomics
Background:
- Microcystin-LR (MCLR) is a potent liver toxin and potential carcinogen.
- Previous studies focused on individual effects of MCLR on liver cells.
- A comprehensive understanding of chronic MCLR exposure effects is needed.
Purpose of the Study:
- To characterize the chronic effects of sublethal microcystin-LR (MCLR) exposure in wild-type mice.
- To integrate gene array analysis, morphology, and plasma chemistry data.
- To identify key molecular pathways and genes affected by chronic MCLR exposure.
Main Methods:
- Mice were exposed to MCLR daily for up to 28 days.
- Gene expression profiling was performed using mouse genechip arrays.
- Quantitative PCR, plasma chemistry, and histological analyses were conducted.
Main Results:
- MCLR exposure led to increased plasma hepatic enzymes and decreased total protein, albumin, and glucose.
- Histological examination revealed hepatokaryomegaly and giant cells in MCLR-treated mice.
- Significant gene transcript changes were observed in pathways related to actin organization, cell cycle, apoptosis, redox, cell signaling, albumin metabolism, and glucose homeostasis.
Conclusions:
- Toxicogenomics identified critical molecular pathways involved in chronic sublethal MCLR exposure.
- Key genes within these pathways were identified and linked to observed cellular and morphological alterations.
- This study provides a comprehensive view of MCLR's chronic effects on liver health.
