Title

The Effect Of Hepatocyte-Specific Glucocorticoid Receptor Loss-Of-Function On Arginase I Expression In The Mouse Liver Urea Cycle

Author(s)

Sean Conway

School Name

South Carolina Governor's School for Science and Mathematics

Grade Level

12th Grade

Presentation Topic

Biochemistry

Presentation Type

Mentored

Mentor

Mentor: Adam Rose, Molecular Metabolic Control, German Cancer Research Center (DKFZ)

Abstract

The glucocorticoid receptor (GR) is known to play a role in gene transcription in nearly every animal cell. However, it is unknown how this relates to the body’s overall function. This research examined two hepatocyte specific GR loss-of-function mice models, one knockout model and one microRNA model, for urea concentration using a urea assay. In both loss-of-function models the concentration was lower than in the controls. With this in mind, the loss-of-function models were examined for gene expression in six urea cycle associated genes using qPCR with cDNA synthesis from RNA samples, and the arginase gene (Arg1) was shown to be most affected. Arginase protein levels were also examined to examine whether it was also a translational problem using the western blot technique. Arginase protein levels were found to be lowered in both loss-of-function models. While these results were obtained from mice models, an understanding of the GR system in humans will also be beneficial. Human Addison’s disease patients, who naturally show a lower GR count, had their serum tested for urea concentration with a urea assay and, like the mice models, showed a significant drop compared to the healthy individuals

Start Date

4-11-2015 9:15 AM

End Date

4-11-2015 9:30 AM

COinS
 
Apr 11th, 9:15 AM Apr 11th, 9:30 AM

The Effect Of Hepatocyte-Specific Glucocorticoid Receptor Loss-Of-Function On Arginase I Expression In The Mouse Liver Urea Cycle

The glucocorticoid receptor (GR) is known to play a role in gene transcription in nearly every animal cell. However, it is unknown how this relates to the body’s overall function. This research examined two hepatocyte specific GR loss-of-function mice models, one knockout model and one microRNA model, for urea concentration using a urea assay. In both loss-of-function models the concentration was lower than in the controls. With this in mind, the loss-of-function models were examined for gene expression in six urea cycle associated genes using qPCR with cDNA synthesis from RNA samples, and the arginase gene (Arg1) was shown to be most affected. Arginase protein levels were also examined to examine whether it was also a translational problem using the western blot technique. Arginase protein levels were found to be lowered in both loss-of-function models. While these results were obtained from mice models, an understanding of the GR system in humans will also be beneficial. Human Addison’s disease patients, who naturally show a lower GR count, had their serum tested for urea concentration with a urea assay and, like the mice models, showed a significant drop compared to the healthy individuals