Conditional Loss of PTEN Leads to Skeletal Abnormalities and Lipoma Formation
Conditional Loss of PTEN Leads to Skeletal Abnormalities and Lipoma Formation
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DOI：
10.1002/mc.20491
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发表时间：
2009-06-01
影响因子：
4.6
通讯作者：
Lo, Su Hao
中科院分区：
文献类型：
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作者：
Hsieh, Shu-Chen;Chen, Nien-Tsu;Lo, Su Hao
为了了解肿瘤抑制因子PTEN在软骨发育中的作用，我们使用Col 2a 1Cre和PTENloxp/loxp小鼠产生了软骨细胞特异性PTEN缺失小鼠。PTEN突变小鼠是可行的和可生育的，尽管如此，随着时间的推移发展脊柱后凸。组织学分析显示，突变小鼠的椎骨和椎间盘更大，因此棘突也比对照小鼠长。此外，生长板更厚，侵入骨小梁区域更深，骨髓脂肪细胞群体在PTEN突变小鼠中更高。此外，生长板，通常不融合在小鼠长骨，融合在PTEN突变体。有趣的是，PTEN小鼠发生脂肪瘤，并显示脂肪组织沿着棘异常积聚。细胞追踪分析已经证实脂肪瘤和一部分脂肪组织来源于Col 2a 1Cre PTENloxp/loxp细胞。进一步的分析表明，PTEN突变的表型可能归因于PTEN在PI 3 K/Akt通路中的负调节作用。(C)2008 Wiley-Liss，Inc.
To understand the role of tumor suppressor PTEN in cartilage development, we have generated chondrocyte specific PTEN deletion mice using Col2a1Cre and PTENloxp/loxp mice. PTEN mutant mice are viable and fertile, nonetheless, develop kyphosis over time. Histological analyses show mutant vertebrae and intervertebral discs are larger and therefore the spines are longer than in control mice. In addition, the growth plates are thicker, invading trabecular bone areas are deeper, and marrow adipocyte populations are higher in PTEN mutant mice. Furthermore, the growth plates, not normally fused in mouse long bones, are fused in PTEN mutants. Intriguingly, PTEN mice develop lipomas and show abnormal accumulation of fat tissues along spines. Cell tracking assays have confirmed that lipomas and a portion of fat tissues were derived from Col2a1Cre PTENloxp/loxp cells. Further analyses have suggested that the phenotypes of PTEN mutant likely attribute to PTEN's negatively regulating role in PI3K/Akt pathway. (C) 2008 Wiley-Liss, Inc.