cn/cn 侏儒小鼠。对应于人类马罗泰克斯型肢端中胚层发育不良（AMDM）的突变体的组织形态计量学、超微结构和放射学研究。

The cn/cn dwarf mouse. Histomorphometric, ultrastructural, and radiographic study in mutants corresponding to human acromesomelic dysplasia Maroteaux type (AMDM).

作者信息

Shapiro Frederic, Barone Lauren, Johnson Andrew, Flynn Evelyn

机构信息

Department of Orthopaedic Surgery, Orthopaedic Research Laboratory, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA 02115, USA.

出版信息

BMC Musculoskelet Disord. 2014 Oct 15;15:347. doi: 10.1186/1471-2474-15-347.

DOI:10.1186/1471-2474-15-347

PMID:25319082

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4219045/

Abstract

BACKGROUND

The cn/cn dwarf mouse is caused by a loss-of-function mutation in the natriuretic peptide receptor 2 (NPR-2) gene which helps positively regulate endochondral longitudinal bone growth. The gene mutation corresponds to that in the human skeletal dysplasia Acromesomelic Dysplasia Maroteaux type (AMDM). This study assesses histomorphometric, ultrastructural and radiographic correlates of the growth abnormality.

METHODS

Ten litters of cn/cn and cn/+littermates at ages ranging from 2.5 to 6.5 weeks were studied by skeletal radiographs, histomorphometry and physeal ultrastructure. Skeletal radiographs were done on 2 cn/cn and 2 cn/+littermates at 5 weeks of age. Humeral, femoral, and tibial lengths were measured from 34 intact bones (17 cn/cn, 17 cn/+) at 2.5 to 6.5 weeks. Growth plate histomorphometry in 50 bones (26 cn/cn and 24 cn/+) determined the hypertrophic zone/entire physeal cartilage ratios in 204 sections (87 cn/+, 117 cn/cn) at 3 time periods (2.5-3, 4-4.5, and 6-6.5 weeks). Electron microscopy assessed 6 cn/cn and 6 cn/+age and site-matched physeal cartilage.

RESULTS

Cn/cn mice were two thirds the size of the cn/+. Cn/cn bones were normal in shape or only minimally deformed except for the radius with mid-diaphyseal bowing. Length ratios of cn/cn humeri, femurs, and tibias were a mean of 0.65 (± 0.03, n = 34, 17 ratios) compared to cn/+bones. The main physeal abnormality was a markedly shortened hypertrophic zone with the ratio of hypertrophic zone to entire physis 0.17 (± 0.063) in the cn/cn and 0.30 (± 0.052) in the cn/+mice. Ratio assessments were similar comparing humeral, femoral, and tibial growth plates as were ratios from each of the 3 time periods. Ultrastructural assessments from the resting zone to the lower hypertrophic zone-metaphyseal junction showed no specific individual cell abnormalities in cn/cn compared to cn/+physes.

CONCLUSIONS

The disorder causes a shortened physeal hypertrophic zone but normal ultrastructure of cn/cn chondrocytes points to abnormality primarily affecting the hypertrophic zone rather than a structural cell or matrix synthesis problem.

摘要

背景

cn/cn 侏儒小鼠是由利钠肽受体 2（NPR - 2）基因功能丧失性突变引起的，该基因有助于正向调节软骨内纵向骨生长。该基因突变与人类骨骼发育异常的 Maroteaux 型肢端中胚层发育不良（AMDM）中的突变相对应。本研究评估生长异常的组织形态计量学、超微结构和影像学相关性。

方法

对 10 窝 2.5 至 6.5 周龄的 cn/cn 和 cn/+同窝小鼠进行骨骼 X 线摄影、组织形态计量学和生长板超微结构研究。对 2 只 5 周龄的 cn/cn 和 2 只 cn/+同窝小鼠进行骨骼 X 线摄影。在 2.5 至 6.5 周龄时，从 34 块完整骨骼（17 块 cn/cn，17 块 cn/+）测量肱骨、股骨和胫骨长度。对 50 块骨骼（26 块 cn/cn 和 24 块 cn/+）进行生长板组织形态计量学分析，确定 3 个时间段（2.5 - 3、4 - 4.5 和 6 - 6.5 周）204 个切片（87 个 cn/+，117 个 cn/cn）中肥大带/整个生长板软骨的比例。电子显微镜评估 6 只 cn/cn 和 6 只 cn/+年龄和部位匹配的生长板软骨。

结果

cn/cn 小鼠的体型是 cn/+小鼠的三分之二。cn/cn 骨骼形状正常或仅轻微变形，除了桡骨有骨干中部弓形弯曲。与 cn/+骨骼相比，cn/cn 肱骨、股骨和胫骨的长度比平均为 0.65（±0.03，n = 34，17 个比例）。主要的生长板异常是肥大带明显缩短，cn/cn 小鼠中肥大带与整个生长板的比例为 0.17（±0.063），cn/+小鼠中为 0.30（±0.052）。比较肱骨、股骨和胫骨生长板的比例评估结果相似，3 个时间段中每个时间段的比例评估结果也相似。从静止区到较低肥大带 - 干骺端交界处的超微结构评估显示，与 cn/+生长板相比，cn/cn 生长板中没有特定的单个细胞异常。