PITX2 gain-of-function induced defects in mouse forelimb development.
PITX2 gain-of-function induced defects in mouse forelimb development.
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DOI：
10.1186/1471-213x-8-25
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发表时间：
2008-02-29
影响因子：
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通讯作者：
Hjalt, Tord A.
中科院分区：
文献类型：
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作者：
Holmberg, Johan;Ingner, Gorel;Johansson, Curt;Leander, Peter;Hjalt, Tord A.
肢体的发育和模式起源于肢体的骨骼元素、肌腱和肌肉之间复杂的相互作用。其中一个参与肢体肌肉形成的基因是同源框转录因子Pitx 2，但它在前肢发育中的作用尚不清楚。Pitx 2在胚胎第12.5天的大多数过早推定前肢肌肉组织中表达，然后在整个胚胎发育到成年骨骼肌中维持。为了进一步研究PITX 2在前肢发育中的作用，我们已经产生了转基因小鼠，其在胚胎第13.5天和第14.5天在发育中的前肢间充质中表现出PITX 2过表达的脉冲。这些小鼠在胚胎发育过程中表现出肱二头肌插入的远端错位，这扭曲了前肢肌肉组织，导致严重的骨骼畸形。骨骼畸形与Leri-Weill软骨发育不良的前臂畸形有一些相似之处。两者合计，肌腱，肌肉和骨骼异常进一步支持Pitx 2在前肢发育中的作用，也可能揭示胚胎发育过程中肢体骨骼元素和肌肉之间的相互作用。
Limb development and patterning originate from a complex interplay between the skeletal elements, tendons, and muscles of the limb. One of the genes involved in patterning of limb muscles is the homeobox transcription factor Pitx2 but its role in forelimb development is uncharacterized. Pitx2 is expressed in the majority of premature presumptive forelimb musculature at embryonic day 12.5 and then maintained throughout embryogenesis to adult skeletal muscle. To further study the role of Pitx2 in forelimb development we have generated transgenic mice that exhibit a pulse of PITX2 over-expression at embryonic day 13.5 and 14.5 in the developing forelimb mesenchyme. These mice exhibit a distal misplacement of the biceps brachii insertion during embryogenesis, which twists the forelimb musculature resulting in severe skeletal malformations. The skeletal malformations have some similarities to the forearm deformities present in Leri-Weill dyschondrosteosis. Taken together, the tendon, muscle, and bone anomalies further support a role of Pitx2 in forelimb development and may also shed light on the interaction between the skeletal elements and muscles of the limb during embryogenesis.