Phenotype profile of a genetic mouse model for Muenke syndrome.
Phenotype profile of a genetic mouse model for Muenke syndrome.
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DOI：
10.1007/s00381-012-1778-9
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发表时间：
2012-09
期刊：
影响因子：
--
通讯作者：
Muenke M
中科院分区：
文献类型：
--
作者：
Nah HD;Koyama E;Agochukwu NB;Bartlett SP;Muenke M
15年前发现的Muenke综合征突变（FGFR 3 P250 R）是最常见的颅缝早闭突变。Muenke综合征的特征是冠状缝骨性结合、面中部发育不全、肢体细微异常和听力丧失。然而，临床表现的范围继续扩大。为了更好地了解Muenke综合征的病理生理学，我们提出了最近几项研究的集体发现，这些研究的特点是Muenke综合征（FgfR 3 P244 R）的遗传等效小鼠模型，并将其与人类表型进行比较。FgfR 3 P244 R突变小鼠表现出面部缝、前上颌骨缝和/或下颌骨缝的过早融合，但很少出现冠状缝。这些小鼠也缺乏典型的肢体表型。另一方面，突变小鼠表现出上颌骨后缩，并伴有前颅底缩短以及蝶间和蝶枕软骨结合过早闭合，类似于人类面中部发育不全。此外，与大多数Muenke综合征患者一样，在所有FgfR 3 P244 R突变小鼠中检测到感音神经性听力损失。它是由Corti器官中细胞命运决定机制的缺陷引起的。这些小鼠还表达了以前在人类中没有描述过的表型，如皮质骨厚度减少，骨小梁发育不良和颞下颌关节结构缺陷。因此，FgfR 3 P244 R小鼠为研究Muenke综合征的一些经典表型的疾病机制和测试新的治疗策略提供了极好的机会。还可以进一步探索小鼠模型，以发现以前未报道但潜在重要的Muenke综合征表型。
The Muenke syndrome mutation (FGFR3P250R), which was discovered 15 years ago, represents the single most common craniosynostosis mutation. Muenke syndrome is characterized by coronal suture synostosis, mid-face hypoplasia, subtle limb anomalies, and hearing loss. However, the spectrum of clinical presentation continues to expand. To better understand the pathophysiology of the Muenke syndrome, we present collective findings from several recent studies that have characterized a genetically equivalent mouse model for Muenke syndrome (FgfR3P244R) and compare them with human phenotypes. FgfR3P244R mutant mice show premature fusion of facial sutures, premaxillary and/or zygomatic sutures, but rarely the coronal suture. The mice also lack the typical limb phenotype. On the other hand, the mutant mice display maxillary retrusion in association with a shortening of the anterior cranial base and a premature closure of intersphenoidal and spheno-occipital synchondroses, resembling human midface hypoplasia. In addition, sensorineural hearing loss is detected in all FgfR3P244R mutant mice as in the majority of Muenke syndrome patients. It is caused by a defect in the mechanism of cell fate determination in the organ of Corti. The mice also express phenotypes that have not been previously described in humans, such as reduced cortical bone thickness, hypoplastic trabecular bone, and defective temporomandibular joint structure. Therefore, the FgfR3P244R mouse provides an excellent opportunity to study disease mechanisms of some classical phenotypes of Muenke syndrome and to test novel therapeutic strategies. The mouse model can also be further explored to discover previously unreported yet potentially significant phenotypes of Muenke syndrome.
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影响因子：
3.5
作者：
Matsushita, Takehiko;Wilcox, William R.;Murakami, Shunichi
通讯作者：
Murakami, Shunichi
影响因子：
2
作者：
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通讯作者：
Marnocha, Anne
影响因子：
0.9
作者：
Keller, Mette K.;Hermann, Nuno V.;Kreiborg, Sven
通讯作者：
Kreiborg, Sven
影响因子：
2.5
作者：
Laurita, Jason;Koyama, Eiki;Nah, Hyun-Duck
通讯作者：
Nah, Hyun-Duck
影响因子：
4.1
作者：
Fakhry, A;Ratisoontorn, C;Nah, HD
通讯作者：
Nah, HD