Abstract

Phenylethanolamine-N-methyltransferase (Pnmt), is the enzyme that catalyzes the conversion of noradrenaline to adrenaline. It has been found in the embryonic heart and in certain adult heart cells, including intrinsic cardiac adrenergic cells, intracardiac neurons, and cardiomyocytes, but their physiological role in the heart is not well understood. To determine the function of Pnmt-expressing cells in the developing heart, a novel genetically-targeted mouse model that causes selective cellular suicide of Pnmt-expressing cells was created by mating Pnmt-Cre Recombinase knock-in mice (PnmtCre/Cre) with ROSA26-eGFP-DTA (R26R+/DTA). The “cellular suicide” allele is the Diptheria Toxin A (DTA) gene fragment. Activation of the DTA suicide allele is dependent upon Cre expression, which is under the control of the endogenous Pnmt gene locus (i.e., expression is restricted to adrenaline-producing “adrenergic” cells). Ongoing studies in Dr. Ebert’s laboratory have shown that Pnmt-Cre/DTA mice have a loss of adrenergic cells in the adrenal gland and begin developing serious cardiac and neurological deficits within one month after birth. The purpose of my project is to examine the potential cardiac consequences of selective adrenergic cell ablation in this model. Aim 1 of this study is to analyze echocardiography data from mice with genetic ablation of adrenergic cells compared to age-matched (littermate) controls over the first 6-months after birth. Preliminary evidence indicates that there is substantial loss of function that progressively worsens with age in the ablation group compared to controls. Aim 2 of this study seeks to uncover evidence of adrenergic cell ablation in the heart using histological and immunofluorescence staining techniques. We predict that these experiments will provide physiological and anatomical evidence showing that Pnmt-expressing cells in the heart make significant contributions to cardiac development and function. This knowledge is expected to increase our basic understanding about the specific roles adrenergic cells play during heart, and could lead to the development of novel treatment strategies for certain types of cardiac defects in the future.

Thesis Completion

2016

Semester

Spring

Thesis Chair

Ebert, Steven

Degree

Bachelor of Science (B.S.)

College

College of Medicine

Department

Burnett School of Biomedical Sciences

Degree Program

Molecular Biology and Microbiology

Location

Orlando (Main) Campus

Language

English

Access Status

Open Access

Length of Campus-only Access

1 year

Release Date

5-1-2017

Included in

Cardiology Commons

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