3 M syndrome is first reported in 1975，which characterized by severe pre- and postnatal growth retardation, skeletal malformation and facial dysmorphism. These three genes (CUL7, OBSL1 and CCDC8) have been identified to be respond for 3 M syndrome, of which CUL7 is accounting for approximately 70%. To date, the molecular mechanism underlying the pathogenesis of 3 M syndrome remains poorly understood. Previous studies showed that no Cul7 mice could survive after birth, because of growth retardation at late gestational stage and respiratory distress after birth. The establishment of the animal model of cartilage specific Cul7 knockout mice (Cul7;Col2a1-CreERT2 mice) has confirmed that Cul7;Col2a1-CreERT2 mice can be selective in a time- and tissue-dependent manner, which can provide an experimental basis for further research on severe genetic diseases related to growth plates. To establish a model of Cul7;Col2a1-CreERT2 mice based on Cre/LoxP system, and to further observe its phenotype and morphological changes in growth plate. The Cul7;Col2a1-CreERT2 mice were taken as the experimental group, while the genotype of Cul7;Col2a1-CreERT2 mice were used as the control group. The gross morphological features and X-ray films of limbs in the two groups were observed every week for 3–6 consecutive weeks, and the length of the mice from nose to the tail, the length of femur and tibia were recorded. In the meantime, The histological morphology of tibial growth plates was compared between the two groups. A preliminary model of Cul7;Col2a1-CreERT2 mice was established. The Cul7;Col2a1-CreERT2 mice had abnormally short and deformed limbs (P<0.05), increased thickness of growth plate, the disorderly arranged chondrocyte columns, decreased number of cells in the proliferation zone, changes in the shape from flat to round, obviously expanded extracellular matrix, and disordered arrangement, thickening and loosening of bone trabecula at the proximal metaphysis of the femur. The knockout of Cul7 gene may affect both the proliferation of chondrocytes and the endochondral osteogenesis, confirming that Cul7 is essential for the normal development of bone in the body.

中文翻译：

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软骨组织特异性CUL7基因敲除小鼠的纵向骨骼生长和生长板形态特征

3M综合征于1975年首次报道，其特点是严重的产前和产后生长迟缓、骨骼畸形和面部畸形。这三个基因（CUL7、OBSL1 和 CCDC8）已被确定对 3M 综合征有反应，其中 CUL7 约占 70%。迄今为止，3M综合征发病机制的分子机制仍知之甚少。此前的研究表明，由于妊娠晚期生长迟缓和出生后呼吸困难，Cul7小鼠无法在出生后存活。软骨特异性Cul7基因敲除小鼠（Cul7;Col2a1-CreERT2小鼠）动物模型的建立，证实了Cul7;Col2a1-CreERT2小鼠具有时间和组织依赖性的选择性，为进一步研究提供了实验基础。与生长板相关的严重遗传疾病的研究。建立基于Cre/LoxP系统的Cul7;Col2a1-CreERT2小鼠模型，并进一步观察其表型和生长板形态变化。以Cul7;Col2a1-CreERT2小鼠为实验组，Cul7;Col2a1-CreERT2基因型小鼠为对照组。每周观察两组四肢大体形态特征和X线片，连续3~6周，记录小鼠鼻至尾长度、股骨、胫骨长度。同时比较两组胫骨生长板的组织学形态。初步建立Cul7;Col2a1-CreERT2小鼠模型。 Cul7;Col2a1-CreERT2小鼠四肢异常短小、畸形（P<0.05），生长板厚度增加，软骨细胞柱排列紊乱，增殖区细胞数量减少，形态由扁转圆，变化明显。细胞外基质扩张，股骨近端干骺端骨小梁排列紊乱、增厚、疏松。 Cul7基因的敲除可能会影响软骨细胞的增殖和软骨内成骨，证实Cul7对于体内骨骼的正常发育至关重要。