The C-terminal region including the MH6 domain of Msx1 regulates skeletal development.
The C-terminal region including the MH6 domain of Msx1 regulates skeletal development.
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包括 Msx1 的 MH6 结构域在内的 C 端区域调节骨骼发育。
DOI：
10.1016/j.bbrc.2020.03.068
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Tanaka E.
中科院分区：
文献类型：
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作者：
Ichihara A;Yasue A;Mitsui SN;Arai D;Minegishi Y;Oyadomari S;Imoto I;Tanaka E.
msx1是人类少齿症的致病基因。虽然传统的MSX1缺陷小鼠会在出生时死亡，但缺乏MSX1 c -末端MH6结构域的突变小鼠（Msx1ΔMH6/ΔMH6）表现出两种不同的表型；腭裂的新生儿纯合子在出生时死亡，而与野生型小鼠相比，腭薄的小鼠存活，颅面发育不良和生长迟缓，大多数小鼠在4-5周龄死亡。在先前报道的由Msx1 MH6结构域杂合缺陷引起的人类少齿症病例中，在枕骨上观察到一个小孔。本研究的目的是验证Msx1 MH6结构域参与体内骨形成的假设。InMsx1ΔMH6/ΔMH6mice，胚胎18.5天颅骨缝合融合延迟，3周龄前后颅径变小，长骨长度减少。股骨骨骺的骨小梁数量没有变化，但骨量、骨密度和骨小梁宽度在Msx1ΔMH6/ΔMH6mice中下降。此外，Msx1ΔMH6/ΔMH6mice松质骨量减少，生长板软骨层变薄。与野生型小鼠相比，主要成骨细胞和软骨细胞分化标志基因mRNA表达水平降低inMsx1ΔMH6/ΔMH6mice。这些发现表明，包括MSX1 MH6结构域在内的c端区域不仅在牙齿发育和腭融合中起重要作用，而且在出生后骨形成中也起重要作用。
MSX1is a causative gene for oligodontia in humans. Although conventionalMsx1-deficient mice die neonatally, a mutant mouse lacking the C-terminus MH6 domain of MSX1 (Msx1ΔMH6/ΔMH6) showed two different phenotypes; newborn homozygotes with cleft palates died neonatally, whereas those with thin palates remained alive and had craniofacial dysplasia and growth retardation compared with wild-type mice, with most mice dying by the age of 4–5 weeks. In a previously reported case of human oligodontia caused by a heterozygous defect of the Msx1 MH6 domain, a small foramen was observed on the occipital bone. The aim of this study was to test the hypothesis that the Msx1 MH6 domain is involved in bone formationin vivo. InMsx1ΔMH6/ΔMH6mice, cranial suture fusion was delayed at embryonic day 18.5, and the anteroposterior cranial diameter was smaller and long bone length was decreased at 3 weeks of age. The femoral epiphysis showed no change in the trabecular number, but decreased bone mass, bone density, and trabecular width in Msx1ΔMH6/ΔMH6mice. In addition, cancellous bone mass was reduced and the cartilage layer in the growth plate was thinner in Msx1ΔMH6/ΔMH6mice. The mRNA expression levels of major osteoblast and chondrocyte differentiation marker genes were decreased inMsx1ΔMH6/ΔMH6mice compared with wild-type mice. These findings suggest that the C-terminal region including the MH6 domain of MSX1 plays important roles not only in tooth development and palatal fusion, but also in postnatal bone formation.