Craniofacial Shape Variation in Twist1+/- Mutant Mice
Craniofacial Shape Variation in Twist1+/- Mutant Mice
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DOI：
10.1002/ar.22899
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发表时间：
2014-05-01
影响因子：
2
通讯作者：
Cray, James J., Jr.
中科院分区：
文献类型：
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作者：
Parsons, Trish E.;Weinberg, Seth M.;Cray, James J., Jr.
颅缝早闭（CS）是一种相对常见的出生缺陷，由一个或多个颅缝过早融合引起。人类遗传学研究已经确定了与CS相关的几个基因。TWIST 1是一种与人类综合征（Saethre-Chotzen综合征）和非综合征形式的CS有关的基因。在这项研究中，一个杂合子Twist 1基因敲除（Twist 1（+/-））小鼠模型被用来研究颅面形状的变化与部分功能丧失。使用几何形态测量方法分析来自微计算机断层扫描的地标数据，以比较15日龄时17只Twist 1（+/-）小鼠和26只Twist 1（+/+）（野生型）同窝对照小鼠之间的颅面形状。结果表明，尽管声称的骨性关节炎严重程度的变化很大，但Twist 1（+/-）小鼠具有一致的颅面畸形模式，影响颅骨的所有主要区域。与Saethre-Chotzen相似，颅骨是尖头的，宽，整体呈短头状。突变小鼠还表现出缩短的颅底和较宽和较短的脸，与冠状面冠状面冠结果表明，这些差异至少部分是Twist 1单倍不足对颅面骨骼发育的直接结果。这项研究提供了一个定量的表型补充，以前对Twist 1进行的发育和分子遗传学研究。这些结果可用于生成关于Twist 1和过早缝合融合对整个颅面骨骼的影响的进一步假设。Anat Rec，297：826-833，2014. (c)2014 Wiley Periodicals，Inc.
Craniosynostosis (CS) is a relatively common birth defect resulting from the premature fusion of one or more cranial sutures. Human genetic studies have identified several genes in association with CS. One such gene that has been implicated in both syndromic (Saethre-Chotzen syndrome) and nonsyndromic forms of CS in humans is TWIST1. In this study, a heterozygous Twist1 knock out (Twist1(+/-)) mouse model was used to study the craniofacial shape changes associated with the partial loss of function. A geometric morphometric approach was used to analyze landmark data derived from microcomputed tomography scans to compare craniofacial shape between 17 Twist1(+/-) mice and 26 of their Twist1(+/+) (wild type) littermate controls at 15 days of age. The results show that despite the purported wide variation in synostotic severity, Twist1(+/-) mice have a consistent pattern of craniofacial dysmorphology affecting all major regions of the skull. Similar to Saethre-Chotzen, the calvarium is acrocephalic and wide with an overall brachycephalic shape. Mutant mice also exhibited a shortened cranial base and a wider and shorted face, consistent with coronal CS associated phenotypes. The results suggest that these differences are at least partially the direct result of the Twist1 haploinsufficiency on the developing craniofacial skeleton. This study provides a quantitative phenotype complement to the developmental and molecular genetic research previously done on Twist1. These results can be used to generate further hypotheses about the effect of Twist1 and premature suture fusion on the entire craniofacial skeleton. Anat Rec, 297:826-833, 2014. (c) 2014 Wiley Periodicals, Inc.