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DNA microarray analysis of the mouse adrenal gland for the detection of hypothermia biomarkers: potential usefulness for forensic investigation.

ABSTRACT: We analyzed the adrenal gland transcriptome of mice killed by hypothermia using DNA microarray technology. A total of 4051 significantly expressed genes were identified; 2015 genes were upregulated and 2036 were downregulated.The FBJ osteosarcoma oncogene was the most upregulated,whereas stearoyl coenzyme A desaturase 3 was the most downregulated. Validation by quantitative polymerase chain reaction revealed that results obtained by both methods were consistent. In the gene set analysis, significant variations were found in nine pathways, and we suggest that transforming growth factor ? and tumor necrosis factor ? would be involved in the pathogenesis of hypothermia. Gene functional category analysis demonstrated the most overexpressed categories in upregulated and downregulated genes were cellular process in biological process, binding in molecular function, and cell and cell part in cellular component. The present study demonstrated acute adrenal responses in hypothermia, and we suggest that understanding adrenal mRNA expression would be useful for hypothermia diagnosis. Furthermore, the present microarray data may also facilitate development of immunohistochemical analysis of human cases. In forensic practice, the combination of macroscopic and microscopic observations with molecular biological analyses would be conducive to more accurate diagnosis of hypothermia. Although this study is aimed at forensic practice, the present data regarding more than 20,000 genes of the adrenal gland would be beneficial to inform future clinical hypothermia research. From the viewpoint of adrenal gene activity, they could contribute to elucidating the pathophysiology of hypothermia.

SUBMITTER: Takamiya M

PROVIDER: S-EPMC3684135 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature

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DNA microarray analysis of the mouse adrenal gland for the detection of hypothermia biomarkers: potential usefulness for forensic investigation.

Takamiya Masataka M Saigusa Kiyoshi K Dewa Koji K

Therapeutic hypothermia and temperature management 20130601 2

We analyzed the adrenal gland transcriptome of mice killed by hypothermia using DNA microarray technology. A total of 4051 significantly expressed genes were identified; 2015 genes were upregulated and 2036 were downregulated.The FBJ osteosarcoma oncogene was the most upregulated,whereas stearoyl coenzyme A desaturase 3 was the most downregulated. Validation by quantitative polymerase chain reaction revealed that results obtained by both methods were consistent. In the gene set analysis, signifi ...[more]

PMID: 23781398

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Project description:Gallbladder mucocele formation is an emerging disease in dogs characterized by increased secretion of condensed granules of gel-forming mucin by the gallbladder epithelium and formation of an abnormally thick mucus that can culminate in obstruction of the bile duct or rupture of the gallbladder. The disease is associated with a high morbidity and mortality and its pathogenesis is unknown. Affected dogs have a significantly increased likelihood of concurrent diagnosis of hyperadrenocorticism, hypothyroidism, and hyperlipidemia. Whether these endocrinopathies represent coincidental primary disease processes that exacerbate gallbladder mucocele formation in predisposed dogs or reflect a concurrent disruption of endocrine and lipid metabolism is unclear. In this study, we investigated a hypothesis that dogs with gallbladder mucocele formation would have a high prevalence of occult and atypical abnormalities in adrenal cortical and thyroid gland function that would suggest the presence of endocrine disruption and provide deeper insight into disease pathogenesis. We performed a case-control study of dogs with and without ultrasonographic diagnosis of gallbladder mucocele formation and profiled adrenal cortical function using a quantitative mass spectrometry-based assay of serum adrenal-origin steroids before and after administration of synthetic cosyntropin. We simultaneously profiled serum thyroid hormone concentrations and evaluated iodine sufficiency by measurement of urine iodine:creatinine ratios (UICR). The studies were complemented by histological examination of archival thyroid tissue and measurements of thyroid gland organic iodine from dogs with gallbladder mucocele formation and control dogs. Dogs with gallbladder mucocele formation demonstrated an exaggerated cortisol response to adrenal stimulation with cosyntropin. A prevalence of 10% of dogs with gallbladder mucocele formation met laboratory-based criteria for suspect or definitive diagnosis of hyperadrenocorticism. A significantly greater number of dogs with gallbladder mucocele formation had basal serum dehydroepiandrosterone (DHEAS) increases compared to control dogs. A high percentage of dogs with gallbladder mucocele formation (26%) met laboratory-based criteria for diagnosis of hypothyroidism, but lacked detection of anti-thyroglobulin antibodies. Dogs with gallbladder mucocele formation had significantly higher UICRs than control dogs. Examination of thyroid tissue from an unrelated group of dogs with gallbladder mucocele formation did not demonstrate histological evidence of thyroiditis or significant differences in content of organic iodine. These findings suggest that dogs with gallbladder mucocele formation have a greater capacity for cortisol synthesis and pinpoint DHEAS elevations as a potential clue to the underlying pathogenesis of the disease. A high prevalence of thyroid dysfunction with absent evidence for autoimmune thyroiditis suggest a disrupted thyroid hormone metabolism in dogs with gallbladder mucocele formation although an influence of non-thyroidal illness cannot be excluded. High UICR in dogs with gallbladder mucocele formation is of undetermined significance, but of interest for further study.

Dataset Information

DNA microarray analysis of the mouse adrenal gland for the detection of hypothermia biomarkers: potential usefulness for forensic investigation.

Publications

DNA microarray analysis of the mouse adrenal gland for the detection of hypothermia biomarkers: potential usefulness for forensic investigation.

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