Mutations in the gene encoding the gap-junctional protein connexin43 (Cx43) are the cause of the human disease oculodentodigital dysplasia (ODDD). The mandible is often affected in this disease, with clinical reports describing both mandibular overgrowth and conversely, retrognathia. These seemingly opposing observations underscore our relative lack of understanding of how ODDD affects mandibular morphology. Using two mutant mouse models that mimic the ODDD phenotype (I130T/+ and G60S/+), we sought to uncover how altered Cx43 function may affect mandibular development. Specifically, mandibles of newborn mice were imaged using micro-CT, to enable statistical comparisons of shape. Tissue-level comparisons of key regions of the mandible were conducted using histomorphology, and we quantified the mRNA expression of several cartilage and bone cell differentiation markers. Both G60S/+ and I130T/+ mutant mice had altered mandibular morphology compared to their wildtype counterparts, and the morphological effects were similarly localized for both mutants. Specifically, the biggest phenotypic differences in mutant mice were focused in regions exposed to mechanical forces, such as alveolar bone, muscular attachment sites, and articular surfaces. Histological analyses revealed differences in ossification of the intramembranous bone of the mandibles of both mutant mice compared to their wildtype littermates. However, chondrocyte organization within the secondary cartilages of the mandible was unaffected in the mutant mice. Overall, our results suggest that the morphological differences seen in G60S/+ and I130T/+ mouse mandibles are due to delayed ossification and suggest that mechanical forces may exacerbate the effects of ODDD on the skeleton.

缝隙连接蛋白连接蛋白43（Cx43）编码基因的突变是人类眼睑数字不典型增生（ODDD）的原因。下颌骨经常受此病影响，临床报告既描述了下颌过度生长又描述了逆行性恋情。这些看似相反的观察结果强调了我们相对缺乏对ODDD如何影响下颌形态的了解。使用模拟ODDD表型的两个突变小鼠模型（I130T / +和G60S / +），我们试图揭示改变的Cx43功能如何影响下颌发育。具体而言，使用micro-CT对新生小鼠的下颌骨进行成像，以进行形状的统计比较。使用组织形态学进行下颌骨关键区域的组织水平比较，我们量化了几种软骨和骨细胞分化标志物的mRNA表达。与野生型对应物相比，G60S / +和I130T / +突变体小鼠的下颌形态均发生了变化，并且两种突变体的形态学效应均相似。具体而言，突变小鼠中最大的表型差异集中在暴露于机械力的区域，例如牙槽骨，肌肉附着部位和关节表面。组织学分析显示，与野生型同窝小鼠相比，这两只突变小鼠的下颌骨膜内骨的骨化差异。但是，在突变小鼠中，下颌骨次级软骨内的软骨细胞组织不受影响。总体，