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Abstract：
Point mutations in KIF22 have been linked to spondyloepimetaphyseal dysplasia with joint laxity, type 2 (SEMDJL2). Skeletal features of SEMDJL2 include short stature and joint laxity. Mechanisms underlying these limb abnormalities are unknown. Here in this manuscript, we have investigated the function of KIF22 in chondrocytes. Quantitative PCR and immunostaining revealed that Kif22 was highly expressed in proliferating-zone growth-plate chondrocytes. Kif22 knockdown resulted in defective mitotic spindle formation and reduced cell proliferation. Forced expression of SEMDJL-associated mutant Kif22 constructs likewise induced abnormal mitotic spindle morphology and reduced proliferation. Mice expressing a KIF22 truncation mutant had shorter growth plates and shorter tibial bones compared to wild-type mice. These results suggest that KIF22 regulates mitotic spindle formation in proliferating chondrocytes thereby linking the stunted longitudinal bone growth observed in SEMDJL2 to failures of chondrocyte division.
摘要：
KIF22中的点突变与关节松弛的脊椎上皮干发育不良有关，类型2（SEMDJL2）。SEMDJL2的骨骼特征包括身材矮小和关节松弛。这些肢体异常的潜在机制尚不清楚。在这份手稿中，我们研究了KIF22在软骨细胞中的功能。定量PCR和免疫染色显示Kif22在增殖区生长板软骨细胞中高表达。Kif22敲低导致有丝分裂纺锤体形成缺陷和细胞增殖减少。SEMDJL相关突变体Kif22构建体的强制表达同样诱导异常有丝分裂纺锤体形态和减少的增殖。与野生型小鼠相比,表达KIF22截短突变体的小鼠具有较短的生长板和较短的胫骨。这些结果表明，KIF22调节增殖软骨细胞中有丝分裂纺锤体的形成，从而将SEMDJL2中观察到的纵向骨骼生长受阻与软骨细胞分裂失败联系起来。
