Overexpression of NGF within the Heart of Transgenic Mice Causes Hyperinnervation, Cardiac Enlargement, and Hyperplasia of Ectopic Cells

Alborz Hassankhani, Mark E. Steinhelper, Mark H. Soonpaa, Ellen B. Katz, Doris A. Taylor, Adriana Andrade-Rozental, Stephen M. Factor, Jacob J. Steinberg, Loren J. Field, Howard J. Federoff

Research output: Contribution to journalArticle

111 Scopus citations

Abstract

Nerve growth factor (NGF) supports the survival of developing sympathetic and a subpopulation of sensory neurons. In the adult it participates in maintenance of the neurotransmitter phenotype of responsive neurons. The amount of NGF synthesized by a given target tissue determines its final innervation density; those developing neurons that fail to receive sufficient NGF undergo apoptosis. In order to examine the ramifications of this principle in the context of a specific target organ, a transgenic mouse model was developed in which NGF expression was increased in developing and adult cardiac tissue by placing a NGF mini-gene under the transcriptional control of the cardiac-specific α-myosin heavy chain promoter. Transgenic mice developed cardiac enlargement secondary to both an increase in myocardial mass and the presence of an abundant ectopic cell population. Immunohistochemical analyses with the neural marker S-100 revealed staining of a subpopulation of ectopic cells, suggesting their derivation from the neural crest. Whereas immunostaining for the neuronal-specific protein neuron-specific enolase demonstrated labeling of another subpopulation of ectopic cells within the heart. Measurements of cardiac tissue catecholamine levels revealed a marked elevation in transgenic mice, consistent with sympathetic hyperinnervation. Analysis of mediastinal sympathetic ganglia revealed increases in both the size and the number of neurons. In this model, increased expression of NGF produced hyperinnervation of the heart, pathological cardiac growth, and the recruitment and/or expansion of an ectopic, neural crest-derived cell type.

Original languageEnglish (US)
Pages (from-to)309-321
Number of pages13
JournalDevelopmental Biology
Volume169
Issue number1
DOIs
StatePublished - May 1995

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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    Hassankhani, A., Steinhelper, M. E., Soonpaa, M. H., Katz, E. B., Taylor, D. A., Andrade-Rozental, A., Factor, S. M., Steinberg, J. J., Field, L. J., & Federoff, H. J. (1995). Overexpression of NGF within the Heart of Transgenic Mice Causes Hyperinnervation, Cardiac Enlargement, and Hyperplasia of Ectopic Cells. Developmental Biology, 169(1), 309-321. https://doi.org/10.1006/dbio.1995.1146