Skeletal analysis of the long bone abnormality (lbab/lbab) mouse, A novel chondrodysplastic C-type natriuretic peptide mutant

Eri Kondo, Akihiro Yasoda, Takehito Tsuji, Toshihito Fujii, Masako Miura, Naotestu Kanamoto, Naohisa Tamura, Hiroshi Arai, Tetsuo Kunieda, Kazuwa Nakao

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11 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)307-318
Number of pages12
JournalCalcified Tissue International
Issue number4
Publication statusPublished - Apr 2012


  • C-type natriuretic peptide
  • Chondrodysplasia
  • Endochondral bone growth
  • Long bone abnormality (lbab)
  • Organ culture

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine
  • Endocrinology


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