| Autor: |
Jewlal, Elizabeth, Barr, Kevin, Laird, Dale W., Willmore, Katherine E. |
| Předmět: |
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| Zdroj: |
Developmental Dynamics; Dec2021, Vol. 250 Issue 12, p1810-1827, 18p |
| Abstrakt: |
Background: We compared skull shape and variation among genetically modified mice that exhibit different levels of connexin43 (Cx43) channel function, to determine whether Cx43 contributes to craniofacial phenotypic robustness. Specifically, we used two heterozygous mutant mouse models (G60S/+ and I130T/+) that, when compared to their wildtype counterparts, have an ~80% and ~50% reduction in Cx43 function, respectively. Results: Both mutant strains showed significant differences in skull shape compared to wildtype littermates and while these differences were more severe in the G60S/+ mouse, shape differences were localized to similar regions of the skull in both mutants. However, increased skull shape variation was observed in G60S/+ mutants only. Additionally, covariation of skull structures was disrupted in the G60S/+ mutants only, indicating that while a 50% reduction in Cx43 function is sufficient to cause a shift in mean skull shape, the threshold for Cx43 function for disrupting craniofacial phenotypic robustness is lower. Conclusions: Collectively, our results indicate Cx43 can contribute to phenotypic robustness of the skull through a nonlinear relationship between Cx43 gap junctional function and phenotypic outcomes. Key Findings: The G60S/+ and I130T/+ mutations both result in a shift in mean skull shape of newborn and 3‐month mice.The differences in skull shape are similarly localized in both mutant mice indicating that the mutations target the same processes of skull development and homeostasis.Cx43 can modulate phenotypic variation of the skull, but only if protein function is reduced beyond a relatively permissive threshold. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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