Title

Physiological and genomic consequences of adrenergic deficiency during embryonic/fetal development in mice: impact on retinoic acid metabolism

Authors

Authors

K. Osuala; C. N. Baker; H. L. Nguyen; C. Martinez; D. Weinshenker;S. N. Ebert

Comments

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Abbreviated Journal Title

Physiol. Genomics

Keywords

hormone; mouse; heart; catecholamine; microarray; ultrasound; PHENYLETHANOLAMINE N-METHYLTRANSFERASE; BETA-CAROTENE; 15, 15'-MONOOXYGENASE; CATECHOLAMINE-SYNTHESIZING ENZYMES; MOUSE; FETAL-DEVELOPMENT; AORTIC-ARCH ANOMALIES; X-RECEPTOR-ALPHA; GENE-EXPRESSION; TARGETED DISRUPTION; RAT-HEART; TYROSINE-HYDROXYLASE; Cell Biology; Genetics & Heredity; Physiology

Abstract

Osuala K, Baker CN, Nguyen HL, Martinez C, Weinshenker D, Ebert SN. Physiological and genomic consequences of adrenergic deficiency during embryonic/fetal development in mice: impact on retinoic acid metabolism. Physiol Genomics 44: 934-947, 2012. First published August 21, 2012; doi:10.1152/physiolgenomics.00180.2011.-Adrenergic hormones are essential for early heart development. To gain insight into understanding how these hormones influence heart development, we evaluated genomic expression changes in embryonic hearts from adrenergic-deficient and wild-type control mice. To perform this study, we used a mouse model with targeted disruption of the Dopamine beta-hydroxylase (Dbh) gene, whose product is responsible for enzymatic conversion of dopamine into norepinephrine. Embryos homozygous for the null allele (Dbh(-/-)) die from heart failure beginning as early as embryonic day 10.5 (E10.5). To assess underlying causes of heart failure, we isolated hearts from Dbh(-/-) and Dbh(+/+) embryos prior to manifestation of the phenotype and examined gene expression changes using genomic Affymetrix 430A 2.0 arrays, which enabled simultaneous evaluation of >22,000 genes. We found that only 22 expressed genes showed a significant twofold or greater change, representing similar to 0.1% of the total genes analyzed. More than half of these genes are associated with either metabolism (31%) or signal transduction (22%). Remarkably, several of the altered genes encode for proteins that are directly involved in retinoic acid (RA) biosynthesis and transport. Subsequent evaluation showed that RA concentrations were significantly elevated by an average of similar to 3-fold in adrenergic-deficient (Dbh(-/-)) embryos compared with controls, thereby suggesting that RA may be an important downstream mediator of adrenergic action during embryonic heart development.

Journal Title

Physiological Genomics

Volume

44

Issue/Number

19

Publication Date

1-1-2012

Document Type

Article

Language

English

First Page

934

Last Page

947

WOS Identifier

WOS:000309551000004

ISSN

1094-8341

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