BMP signaling plays pleiotropic roles in various tissues during embryogenesis and after birth. We have previously generated a constitutively activated Acvr1(ca-Acvr1) transgenic mouse line (line L35) through pronuclei injection to investigate impacts of enhanced BMP signaling in a tissue specific manner. However, line L35 shows a restricted expression pattern of the transgene. Here, we generated another ca-Acvr1 transgenic line, line A11, using embryonic stem (ES) transgenesis. The generated line A11 shows distinctive phenotypes from line L35, along with very limited expression levels of the transgene. When the transgene is activated in the neural crest cells in a Cre-dependent manner, line A11 exhibits cleft palate and shorter jaws, while line L35 develops ectopic cartilages and highly hypomorphic facial structures. When activated in limb buds, line A11 develops organized but smaller limb skeletal structures, while line L35 forms disorganized limbs with little mineralization. Additionally, no heterotopic ossification (HO) is identified in line A11 when bred with NFATc1-Cre mice even after induction of tissue injury, which is an established protocol for HO for line L35. Therefore, the newly generated conditional ca-Acvr1 mouse line A11 provides an additional resource to dissect highly context dependent functions of BMP signaling in development and disease.

中文翻译：

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通过 BMP 受体产生具有条件激活信号的新小鼠系，ACVR1：一种表征 BMP 功能多效性作用的工具

BMP 信号在胚胎发生过程和出生后的各种组织中发挥多效性作用。我们之前通过原核注射产生了组成型激活的Acvr1 ( ca-Acvr1 ) 转基因小鼠系 (L35 系)，以研究增强的 BMP 信号以组织特异性方式的影响。然而，L35 行显示了转基因的受限表达模式。在这里，我们生成了另一个ca-Acvr1转基因株系A11，使用胚胎干（ES）转基因。生成的 A11 系显示出来自 L35 系的独特表型，以及非常有限的转基因表达水平。当转基因以依赖于 Cre 的方式在神经嵴细胞中被激活时，A11 系表现出腭裂和更短的下巴，而 L35 系则出现异位软骨和高度变形的面部结构。当在肢芽中被激活时，A11 线会形成有组织但较小的肢体骨骼结构，而 L35 线会形成杂乱无章的肢体，几乎没有矿化。此外，即使在诱导组织损伤后，与NFATc1-Cre小鼠繁殖时，A11 系中也没有发现异位骨化 (H2O) ，这是 L35 系 H2O 的既定方案。因此，新生成的条件ca-Acvr1小鼠线 A11 提供了一个额外的资源来剖析 BMP 信号在发育和疾病中的高度上下文依赖性功能。