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

    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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