Introduction: Genetic disorders are usually characterised by subjective morphological traits. Mouse models should represent the human situation but it is difficult to translate morphology traits from one species to another. Thus, there is a demand to objectively assess morphological traits. Geometric morphometrics is a mathematical tool to evaluate morphology based on normalised three-dimensional coordinates. Here we use geometric morphometrics to compare the morphology of SOST knockout (SOST KO) mice with respective wild type (WT) mice and relate the symptoms to human sclerosteosis.
Materials and Methods: We analysed the morphological differences between six mice skulls lacking sclerostin and six respective wild type controls (ethically approved). A total of 27 landmark coordinates per skull were obtained based on microcomputed tomography surfaces. Generalized Procrustes analysis superimposes the skull shapes, allowing computing and visualizing morphological dissimilarities and size. Statistical evaluation of morphological differences was done by principal component analysis. We further computed the asymmetry by reflected relabelling and calculated the mandibular prognathism by comparison of distances.
Results: Generalized Procrustes analysis revealed that SOST KO mice have a larger centroid size (WT: mean 1587±11; SOST KO: 1654±15), and are more asymmetric (SOST KO: 0.000669; WT: 0.000429 [Procrustes sum of squares]) than WT mice. Principal component analysis showed that SOST KO caused curved skulls and a smaller diameter of the foramen magnum in relation to WT mice. Moreover, SOST KO mice have dental and skeletal mandibular prognathism in relation to their WT littermates.
Conclusion: Geometric morphometrics is a mathematical tool to discover morphological dissimilarities in the skull of genetically manipulated mice. This method allows visualizing morphological differences in mice that represent human genetic disorders.
14 May 2016 - 17 May 2016