AJP - Endocrinology and Metabolism, Vol 262, Issue 4 E524-E531, Copyright © 1992 by American Physiological Society
Atrial natriuretic peptide synthesis in atrial tumors of transgenic mice
D. G. Gardner, M. J. Camargo, R. R. Behringer, R. L. Brinster, J. D. Baxter, S. A. Atlas, J. H. Laragh and C. F. Deschepper
Department of Medicine, University of California, San Francisco 94143.
Transgenic mice harboring a chimeric gene linking mouse protamine 1
5'-flanking sequence to the coding sequence of the simian virus 40
T-antigen develop spontaneous rhabdomyosarcomas of the right atria. The
presence of the tumors is accompanied by dramatic elevations in plasma
atrial natriuretic peptide (ANP) immunoreactivity (1,698 +/- 993 vs. 60 +/-
18 fmol/ml for controls) and hematocrit (56 +/- 8 vs. 51 +/- 2 for
controls). The immunoreactive ANP (irANP) present in the tumors is similar
in size to irANP found in normal mouse atria. ANP mRNA transcripts present
in the tumors also appear to be very similar in overall size and 5'-termini
to those produced in normal cardiac tissue. Microscopically, the tumors are
composed of a disorganized array of densely packed abnormal-appearing
cells. Immunocytochemistry and in situ hybridization analysis reveal
considerable heterogeneity in ANP gene expression. ANP peptide and mRNA are
detectable throughout the parenchyma of the tumors, but absolute levels of
expression vary widely among different cells in the population. These
tumors represent a potentially valuable model for the study of
inappropriate ANP secretion and may provide a tissue source for the
development of an ANP-producing atrial cell line.
