Details

Autor(en) / Beteiligte

• Moore, Alyssa C
• Jewlal, Elizabeth
• Barr, Kevin
• Laird, Dale W
• Willmore, Katherine E

Titel

Interactions Between Channel Function, Cellular Differentiation, and Morphology in the Mandibles of Two Connexin‐43 Mutant Mouse Models

Ist Teil von

• The FASEB journal, 2019-04, Vol.33 (S1), p.774.15-774.15

Ort / Verlag

The Federation of American Societies for Experimental Biology

Erscheinungsjahr

2019

Link zum Volltext

Quelle

Wiley Online Library

Beschreibungen/Notizen

• Background Mutations in the gene encoding connexin‐43 (Cx43) can result in the human disease oculodentodigital dysplasia (ODDD), which has a strong craniofacial phenotype, including microphthalmia, a narrowed nose, and an increased incidence of cleft palate. The literature on the human condition of ODDD documents a mandibular phenotype including macrognathia and widened alveolar ridges; however, the mandibular phenotype has yet to be studied in detail in mouse models of ODDD. As well, a stepwise link between the amount of functional Cx43 protein, cellular differentiation, and phenotype has been found in heterozygous and homozygous Cx43 knockout mice, but this stepwise progression in Cx43 functionality, cellular changes, and phenotypic changes has yet to be investigated in mouse models of ODDD. Therefore, the purpose of this project is to determine the relationship between Cx43 function, celular differentiation, and mandibular morphology. Methods We used two mouse models with mutations in the gene encoding for Cx43 which have 20% channel functionality and a severe ODDD phenotype (Cx43G60S/+) or 50% channel functionality and a moderate ODDD phenotype (Cx43I130T/+), respectively. Homologous landmark data were collected from microCT images of newborn hemimandibles and analyzed with geometric morphometric analyses to quantify and visualize mandibular shape changes between mutants and wildtype littermates. General mandibular histomorphology will be qualitatively assessed using Safranin‐O/Fast Green staining and compared among genotypes. We will also quantify expression of chondrocyte, osteoblast, osteoclast, and osteocyte differentiation markers in these mutant mice and their wildtype littermates using qRT‐PCR. With these procedures, we hope to gain an understanding of the relationship between Cx43 function, cellular differentiation, and mandibular morphology. Preliminary Results Cx43G60S/+ mice display significant alterations to mandibular shape and size when compared to their wildtype littermates. The changes to shape and size cluster around the incisor alveolar process, coronoid process, angular process, condylar process, and mental and mandibular foramina in Cx43G60S/+ mice. Potential drivers for these size and shape changes include delayed ossification and the interaction of different modes of ossification in secondary cartilage. Significance & Future Directions Our preliminary work confirms that altered Cx43 function results in altered mandibular morphology. Ongoing studies are focused on determining if cellular differentiation is altered in the bone and cartilage of our mutant mandibles and if these cellular changes can explain the phenotypic changes observed. Support or Funding Information This study was funded by NSERC. This is from the Experimental Biology 2019 Meeting. There is no full text article associated with this published in The FASEB Journal.