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.
| Original language | English |
|---|---|
| Pages (from-to) | 307-318 |
| Number of pages | 12 |
| Journal | Calcified Tissue International |
| Volume | 90 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - Apr 2012 |
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Keywords
- C-type natriuretic peptide
- Chondrodysplasia
- Endochondral bone growth
- Long bone abnormality (lbab)
- Organ culture
ASJC Scopus subject areas
- Orthopedics and Sports Medicine
- Endocrinology, Diabetes and Metabolism
- Endocrinology
Cite this
Skeletal analysis of the long bone abnormality (lbab/lbab) mouse, A novel chondrodysplastic C-type natriuretic peptide mutant. / Kondo, Eri; Yasoda, Akihiro; Tsuji, Takehito; Fujii, Toshihito; Miura, Masako; Kanamoto, Naotestu; Tamura, Naohisa; Arai, Hiroshi; Kunieda, Tetsuo; Nakao, Kazuwa.
In: Calcified Tissue International, Vol. 90, No. 4, 04.2012, p. 307-318.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Skeletal analysis of the long bone abnormality (lbab/lbab) mouse, A novel chondrodysplastic C-type natriuretic peptide mutant
AU - Kondo, Eri
AU - Yasoda, Akihiro
AU - Tsuji, Takehito
AU - Fujii, Toshihito
AU - Miura, Masako
AU - Kanamoto, Naotestu
AU - Tamura, Naohisa
AU - Arai, Hiroshi
AU - Kunieda, Tetsuo
AU - Nakao, Kazuwa
PY - 2012/4
Y1 - 2012/4
N2 - 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.
AB - 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.
KW - C-type natriuretic peptide
KW - Chondrodysplasia
KW - Endochondral bone growth
KW - Long bone abnormality (lbab)
KW - Organ culture
UR - http://www.scopus.com/inward/record.url?scp=84859909527&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84859909527&partnerID=8YFLogxK
U2 - 10.1007/s00223-011-9567-0
DO - 10.1007/s00223-011-9567-0
M3 - Article
C2 - 22271248
AN - SCOPUS:84859909527
VL - 90
SP - 307
EP - 318
JO - Calcified Tissue International
JF - Calcified Tissue International
SN - 0171-967X
IS - 4
ER -