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PMID:11259675

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Citation

Chusho, H, Tamura, N, Ogawa, Y, Yasoda, A, Suda, M, Miyazawa, T, Nakamura, K, Nakao, K, Kurihara, T, Komatsu, Y, Itoh, H, Tanaka, K, Saito, Y, Katsuki, M and Nakao, K (2001) Dwarfism and early death in mice lacking C-type natriuretic peptide. Proc. Natl. Acad. Sci. U.S.A. 98:4016-21

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.

Links

PubMed PMC31171 Online version:10.1073/pnas.071389098

Keywords

Animals; Bone and Bones/metabolism; Chondrocytes/metabolism; Chondrocytes/physiology; Disease Models, Animal; Dwarfism/metabolism; Dwarfism/mortality; Female; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Natriuretic Peptide, C-Type/deficiency; Natriuretic Peptide, C-Type/genetics; Natriuretic Peptide, C-Type/metabolism; Ossification, Heterotopic

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:ANFC

involved_in

GO:0003419: growth plate cartilage chondrocyte proliferation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:ANFC

involved_in

GO:0003418: growth plate cartilage chondrocyte differentiation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:ANFC

acts_upstream_of

GO:0006182: cGMP biosynthetic process

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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