Preparing your results

Our searching services are busy right now. Your search will reload in five seconds.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Disruption of the nonneuronal tph1 gene demonstrates the importance of peripheral serotonin in cardiac function.

http://www.ncbi.nlm.nih.gov/pubmed/14597720

Serotonin (5-HT) controls a wide range of biological functions. In the brain, its implication as a neurotransmitter and in the control of behavioral traits has been largely documented. At the periphery, its modulatory role in physiological processes, such as the cardiovascular function, is still poorly understood. The rate-limiting enzyme of 5-HT synthesis, tryptophan hydroxylase (TPH), is encoded by two genes, the well characterized tph1 gene and a recently identified tph2 gene. In this article, based on the study of a mutant mouse in which the tph1 gene has been inactivated by replacement with the beta-galactosidase gene, we establish that the neuronal tph2 is expressed in neurons of the raphe nuclei and of the myenteric plexus, whereas the nonneuronal tph1, as detected by beta-galactosidase expression, is in the pineal gland and the enterochromaffin cells. Anatomic examination of the mutant mice revealed larger heart sizes than in wild-type mice. Histological investigation indicates that the primary structure of the heart muscle is not affected. Hemodynamic analyses demonstrate abnormal cardiac activity, which ultimately leads to heart failure of the mutant animals. This report links loss of tph1 gene expression, and thus of peripheral 5-HT, to a cardiac dysfunction phenotype. The tph1-/- mutant may be valuable for investigating cardiovascular dysfunction observed in heart failure in humans.

Pubmed ID: 14597720 RIS Download

Mesh terms: Alleles | Animals | Chromaffin Cells | Chromatography, High Pressure Liquid | Embryo, Mammalian | Genotype | Humans | Hydroxyindoleacetic Acid | Immunohistochemistry | In Situ Hybridization | Mice | Mice, Mutant Strains | Mice, Transgenic | Models, Genetic | Mutation | Myenteric Plexus | Myocardium | Phenotype | RNA, Messenger | Raphe Nuclei | Serotonin | Stem Cells | Tissue Distribution | Tryptophan Hydroxylase | beta-Galactosidase

Research resources used in this publication

None found

Research tools detected in this publication

None found

Data used in this publication

None found

Associated grants

None

Mouse Genome Informatics (Data, Gene Annotation)

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.