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Dwarfism and early death in mice lacking C-type natriuretic peptide
- Source :
- Proceedings of the National Academy of Sciences. 98:4016-4021
- Publication Year :
- 2001
- Publisher :
- Proceedings of the National Academy of Sciences, 2001.
-
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.
- Subjects :
- Male
medicine.medical_specialty
Programmed cell death
medicine.drug_class
Dwarfism
Mice, Transgenic
Biology
Bone and Bones
Muscle hypertrophy
Mice
Chondrocytes
Internal medicine
Natriuretic peptide
medicine
Animals
Achondroplasia
Endochondral ossification
Multidisciplinary
Ossification, Heterotopic
Natriuretic Peptide, C-Type
Biological Sciences
medicine.disease
Endochondral bone growth
Mice, Inbred C57BL
Disease Models, Animal
Endocrinology
Female
Homeostasis
Subjects
Details
- ISSN :
- 10916490 and 00278424
- Volume :
- 98
- Database :
- OpenAIRE
- Journal :
- Proceedings of the National Academy of Sciences
- Accession number :
- edsair.doi.dedup.....4a8a6e86beb0ceb1783c369ecf47bf6d