Gene Expression Analysis of Feline Thyroid Tissue and Blood from Cats with Evidence of Mild or Marked Hyperthyroidism Reveals Potential Molecular Causes of the Disease and Identifies Future Routes for Intervention
Melendez L. and Al-Murrani S.
Conference Proceedings, (2011). American College of Veterinary Internal Medicine:
Hyperthyroidism is a disorder resulting from the excessive production and secretion of T4 and T3 by the thyroid gland. Although the disorder and its pathological lesions have been well studied and described the cause remains illusive.
Whole blood and solid tissue samples from non-diseased, severe disease and mild disease cats based on T4 levels and thyroid histology were used in this study. Whole blood samples from 29 non-disease cats, 28 severe disease cats and 17 mild disease cats as well as solid thyroid tissue samples from 30 non-disease cats, 31 severe disease cats and 27 mild disease cats were collected and processed. The resulting total RNA samples were used for GeneChip analysis using our custom feline gene chip designed by Affymetrix. Data analysis was performed using The Parteks GS software for Gene Expression data. The Robust Multichip Average algorithm was used for background adjustment, normalization, and probe-level summarization of the raw data. ANOVA analysis was performed to find significant differentially expressed genes with a minimal False Discovery Rate control of 0.1 and a fold change of 1.3 in each direction.
During the mild disease state, pathways associated with DNA damage and apoptosis are most prominent. At later stages when the histopathological disease is more severe in addition to the aforemen- tioned pathways others associated with TGF-beta signaling, cell adhesion and extracellular matrix remodeling take more prominence.
The analysis of this unique data set generated from the use of our proprietary GeneChip revealed molecular mechanisms that are associated with the transition from non-disease, to mild disease to severe disease, in the thyroid tissue as well as the blood. These mechanisms could provide insights into the causes of the disease and identify potential new therapeutic and diagnostic targets.