Fibrodysplasia ossificans progressiva: mechanisms and models of skeletal metamorphosis.
Fibrodysplasia ossificans progressiva: mechanisms and models of skeletal metamorphosis.
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DOI：
10.1242/dmm.010280
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发表时间：
2012-11
影响因子：
4.3
通讯作者：
Shore EM
中科院分区：
文献类型：
--
作者：
Kaplan FS;Chakkalakal SA;Shore EM
进行性骨化性纤维发育不良（FOP；MIM #135100）是一种使人衰弱的结缔组织变态遗传性疾病。其特征是胚胎骨骼发育过程中大脚趾畸形，以及出生后进行性异位软骨内骨化（HEO），从而导致异位骨第二骨骼的形成。具有 FOP 这些经典临床特征的个体在编码 ACVR1（也称为 ALK2）（一种骨形态发生蛋白 (BMP) I 型受体）的基因中具有相同的杂合激活突变 (c.617G>A；R206H)。这种 ACVR1 突变引起的疾病活动还取决于细胞和组织生理学的改变，这可以在高保真动物模型的背景下得到最好的理解。最近，我们开发了一种 FOP (Acvr1R206H/+) 敲入小鼠模型，它可以概括人类疾病，并为测试和开发有效疗法提供了有价值的新工具。 FOP 敲入小鼠以及果蝇、斑马鱼、鸡和小鼠的其他模型为理解 BMP 信号传导和解决疾病机制的突出问题提供了一系列工具，这些疾病机制不仅与 FOP 相关，还与再生医学和组织变态相关的各种疾病相关。
Fibrodysplasia ossificans progressiva (FOP; MIM #135100) is a debilitating genetic disorder of connective tissue metamorphosis. It is characterized by malformation of the great (big) toes during embryonic skeletal development and by progressive heterotopic endochondral ossification (HEO) postnatally, which leads to the formation of a second skeleton of heterotopic bone. Individuals with these classic clinical features of FOP have the identical heterozygous activating mutation (c.617G>A; R206H) in the gene encoding ACVR1 (also known as ALK2), a bone morphogenetic protein (BMP) type I receptor. Disease activity caused by this ACVR1 mutation also depends on altered cell and tissue physiology that can be best understood in the context of a high-fidelity animal model. Recently, we developed such a knock-in mouse model for FOP (Acvr1R206H/+) that recapitulates the human disease, and provides a valuable new tool for testing and developing effective therapies. The FOP knock-in mouse and other models in Drosophila, zebrafish, chickens and mice provide an arsenal of tools for understanding BMP signaling and addressing outstanding questions of disease mechanisms that are relevant not only to FOP but also to a wide variety of disorders associated with regenerative medicine and tissue metamorphosis.
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DOI：
10.2106/00004623-200312000-00010
发表时间：
2003-12-01
影响因子：
5.3
作者：
Glaser, DL;Economides, AN;Shore, EM
通讯作者：
Shore, EM
影响因子：
5.1
作者：
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通讯作者：
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影响因子：
4.8
作者：
Fukuda, Toru;Kohda, Masakazu;Katagiri, Takenobu
通讯作者：
Katagiri, Takenobu
影响因子：
6.2
作者：
Billings, Paul C.;Fiori, Jennifer L.;Kaplan, Frederick S.
通讯作者：
Kaplan, Frederick S.
DOI：
10.1302/0301-620x.64b1.7068725
发表时间：
1982-01-01
影响因子：
--
作者：
CONNOR, JM;EVANS, DAP
通讯作者：
EVANS, DAP