Skeletal Analysis of the Long Bone Abnormality (lbab/lbab) Mouse, A Novel Chondrodysplastic C-Type Natriuretic Peptide Mutant
Skeletal Analysis of the Long Bone Abnormality (lbab/lbab) Mouse, A Novel Chondrodysplastic C-Type Natriuretic Peptide Mutant
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DOI：
10.1007/s00223-011-9567-0
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发表时间：
2012-04-01
影响因子：
4.2
通讯作者：
Nakao, Kazuwa
中科院分区：
文献类型：
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作者：
Kondo, Eri;Yasoda, Akihiro;Nakao, Kazuwa
长骨异常（lbab/lbab）是一种侏儒小鼠。最近的研究表明，该表型是由编码小鼠C型利钠肽（CNP）的Nppc基因的自发突变引起的。在这项研究中，我们分析了lbab/lbab小鼠的软骨发育不良骨骼表型。出生时，lbab/lbab小鼠只比野生型小鼠略矮。然而，lbab/lbab小鼠并没有经历生长突增，它们最终的身体和骨骼长度仅与野生型小鼠的60%相似。组织学分析显示，lbab/lbab小鼠的生长板，特别是肥大的软骨细胞层，比野生型小鼠明显更薄。CNP在lbab/lbab小鼠软骨中的过表达恢复了其变薄的生长板，随后完全挽救了其受损的软骨内骨生长。此外，lbab/lbab小鼠的骨体积严重降低，并通过CNP过表达恢复。另一方面，lbab/+小鼠的生长板厚度与野生型小鼠无差异;因此，在lbab/+小鼠中未观察到软骨内骨生长受损。在器官培养实验中，胎仔lbab/lbab小鼠的胫骨外植体显著短于lbab/+小鼠的胫骨外植体，并且通过加入10（-7）M CNP延长至与用相同剂量CNP处理的lbab/+小鼠相同的程度。这些结果表明，lbab/lbab是一种新型的软骨发育不良小鼠模型，由CNP对软骨内骨化的作用不足引起。
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 similar to 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.