Dwarfism and early death in mice lacking C-type natriuretic peptide
Top Cited Papers
- 20 March 2001
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 98 (7) , 4016-4021
- https://doi.org/10.1073/pnas.071389098
Abstract
Longitudinal bone growth is determined by endochondral ossification that occurs as chondrocytes in the cartilaginous growth plate undergo proliferation, hypertrophy, cell death, and osteoblastic replacement. The natriuretic peptide family consists of three structurally related endogenous ligands, atrial, brain, and C-type natriuretic peptides (ANP, BNP, and CNP), and is thought to be involved in a variety of homeostatic processes. To investigate the physiological significance of CNP in vivo, we generated mice with targeted disruption of CNP (Nppc(-/-) mice). The Nppc(-/-) mice show severe dwarfism as a result of impaired endochondral ossification. They are all viable perinatally, but less than half can survive during postnatal development. The skeletal phenotypes are histologically similar to those seen in patients with achondroplasia, the most common genetic form of human dwarfism. Targeted expression of CNP in the growth plate chondrocytes can rescue the skeletal defect of Nppc(-/-) mice and allow their prolonged survival. This study demonstrates that CNP acts locally as a positive regulator of endochondral ossification in vivo and suggests its pathophysiological and therapeutic implication in some forms of skeletal dysplasia.Keywords
This publication has 34 references indexed in Scilit:
- Intestinal Secretory Defects and Dwarfism in Mice Lacking cGMP-Dependent Protein Kinase IIScience, 1996
- Two Cardiac Natriuretic Peptide Genes (Atrial Natriuretic Peptide and Brain Natriuretic Peptide) are Organized in Tandem in the Mouse and Human GenomesJournal of Molecular and Cellular Cardiology, 1996
- Stop codon FGFR3 mutations in thanatophoric dwarfism type 1Nature Genetics, 1995
- Thanatophoric dysplasia (types I and II) caused by distinct mutations in fibroblast growth factor receptor 3Nature Genetics, 1995
- Molecular cloning of the complementary DNA and gene that encode mouse brain natriuretic peptide and generation of transgenic mice that overexpress the brain natriuretic peptide gene.Journal of Clinical Investigation, 1994
- SIGNAL TRANSDUCTION BY GUANYLYL CYCLASESAnnual Review of Biochemistry, 1991
- ATRIAL NATRIURETIC FACTOR AND RELATED PEPTIDE HORMONESAnnual Review of Biochemistry, 1991
- Selective Activation of the B Natriuretic Peptide Receptor by C-Type Natriuretic Peptide (CNP)Science, 1991
- Physiological Role of Silent Receptors of Atrial Natriuretic FactorScience, 1987
- Achondroplasia and hypochondroplasia. Comments on frequency, mutation rate, and radiological features in skull and spine.Journal of Medical Genetics, 1979