title: Skeletal analysis of the long bone abnormality (lbab/lbab) mouse, a novel chondrodysplastic C-type natriuretic peptide mutant.
abstract: Long bone abnormality (lbab/lbab) is a strain of dwarf mice. Recent studies revealed that the phenotype is caused by a spontaneous mutation in the Nppc gene, which encodes mouse C-type natriuretic peptide (CNP). In this study, we analyzed the chondrodysplastic skeletal phenotype of lbab/lbab mice. At birth, lbab/lbab mice are only slightly shorter than their wild-type littermates. Nevertheless, lbab/lbab mice do not undergo a growth spurt, and their final body and bone lengths are only ~60% of those of wild-type mice. Histological analysis revealed that the growth plate in lbab/lbab mice, especially the hypertrophic chondrocyte layer, was significantly thinner than in wild-type mice. Overexpression of CNP in the cartilage of lbab/lbab mice restored their thinned growth plate, followed by the complete rescue of their impaired endochondral bone growth. Furthermore, the bone volume in lbab/lbab mouse was severely decreased and was recovered by CNP overexpression. On the other hand, the thickness of the growth plate of lbab/+ mice was not different from that of wild-type mice; accordingly, impaired endochondral bone growth was not observed in lbab/+ mice. In organ culture experiments, tibial explants from fetal lbab/lbab mice were significantly shorter than those from lbab/+ mice and elongated by addition of 10(-7) M CNP to the same extent as lbab/+ tibiae treated with the same dose of CNP. These results demonstrate that lbab/lbab is a novel mouse model of chondrodysplasia caused by insufficient CNP action on endochondral ossification.
authors.affiliation: Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Eri
authors.initials: E
authors.lastname: Kondo
authors.forename: Akihiro
authors.initials: A
authors.lastname: Yasoda
authors.forename: Takehito
authors.initials: T
authors.lastname: Tsuji
authors.forename: Toshihito
authors.initials: T
authors.lastname: Fujii
authors.forename: Masako
authors.initials: M
authors.lastname: Miura
authors.forename: Naotestu
authors.initials: N
authors.lastname: Kanamoto
authors.forename: Naohisa
authors.initials: N
authors.lastname: Tamura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Arai
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Kunieda
authors.forename: Kazuwa
authors.initials: K
authors.lastname: Nakao
mesh_terms: D000818:Animals; D001846:Bone Development / Q000235:genetics*; D001848:Bone Diseases, Developmental / Q000235:genetics*; D006132:Growth Plate / Q000002:abnormalities; D051379:Mice; D008815:Mice, Inbred Strains; D020098:Natriuretic Peptide, C-Type / Q000235:genetics*; D009924:Organ Culture Techniques; D010012:Osteogenesis / Q000235:genetics; D013977:Tibia / Q000002:abnormalities
chemical_list: D020098:Natriuretic Peptide, C-Type