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首页> 外文期刊>American Journal of Physiology >Depletion of cartilage collagen fibrils in mice carrying a dominant negative Col2a1 transgene affects chondrocyte differentiation.
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Depletion of cartilage collagen fibrils in mice carrying a dominant negative Col2a1 transgene affects chondrocyte differentiation.

机译：携带显性负Col2a1转基因的小鼠的软骨胶原原纤维耗竭会影响软骨细胞的分化。

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摘要

We have generated transgenic mice harboring the deletion of exon 48 in the mouse alpha1(II) procollagen gene (Col2a1). This was the first dominant negative mutation identified in the human alpha1(II) procollagen gene (COL2A1). Patients carrying a single allele with this mutation suffer from a severe skeletal disorder called spondyloepiphyseal dysplasia congenita (SED). Transgenic mice phenotype was neonatally lethal with severe respiratory failure, short bones, and cleft palate. Transgene mRNA was expressed at high levels. Growth plate cartilage of transgenic mice presented morphological abnormalities and reduced number of collagen type II fibrils. Chondrocytes carrying the mutation showed altered expression of several differentiation markers, like fibroblast growth factor receptor 3 (Fgfr3), Indian hedgehog (Ihh), runx2, cyclin-dependent kinase inhibitor P21CIP/WAF (Cdkn1a), and collagen type X (Col10a1), suggesting that a defective extracellular matrix (ECM) depleted of collagen fibrils affects chondrocytes differentiation and that this defect participates in the reduced endochondral bone growth observed in chondrodysplasias caused by mutations in COL2A1.
机译：我们已经生成了转基因小鼠，该小鼠在小鼠alpha1（II）前胶原基因（Col2a1）中具有外显子48的缺失。这是在人类alpha1（II）前胶原基因（COL2A1）中确定的第一个显性负突变。携带具有此突变的单个等位基因的患者患有严重的骨骼疾病，称为先天性脊柱干pi发育不良（SED）。转基因小鼠的表型具有致命的呼吸衰竭，短骨和c裂的新生儿致死性。转基因mRNA高水平表达。转基因小鼠的生长板软骨表现出形态学异常和II型胶原原纤维数量减少。携带突变的软骨细胞显示出几种分化标记物的表达改变，例如成纤维细胞生长因子受体3（Fgfr3），印度刺猬（Ihh），runx2，细胞周期蛋白依赖性激酶抑制剂P21CIP / WAF（Cdkn1a）和X型胶原（Col10a1），提示缺损的胶原纤维的细胞外基质（ECM）会影响软骨细胞的分化，并且这种缺陷参与了由COL2A1突变引起的软骨发育不良中所观察到的软骨内骨生长减少。

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