Anatomical similarity between the Sost‐knockout mouse and sclerosteosis in humans

Abstract

Sclerosteosis, a rare autosomal recessive genetic disorder caused by a mutation of the Sost gene, manifests in the facial skeleton by gigantism, facial distortion, mandibular prognathism, cranial nerve palsy, and, in extreme cases, compression of the medulla oblongata. Mice lacking sclerostin reflect some symptoms of sclerosteosis, but this is the first report of the effect on the facial skeleton. We used geometric morphometrics (GMM) to analyze the deformations of the murine facial skeleton from the wild-type to the Sost gene knockout. Landmark coordinates were obtained by surface reconstructions from micro-computed tomography. Centroid size, principal component scores in shape space and form space, and asymmetry were computed by the standard GMM formulas, and dental and skeletal jaw lengths were examined as ratios. We show here that, compared to wild type controls, mice lacking Sost have larger centroid size (effect size, p-value: 4.59, <.001), higher mean asymmetry (1.14, .065), dental and skeletal mandibular prognathism (1.36, .010 and 5.92, <.001), a smaller foramen magnum (−1.71, .015), and calvaria that are more highly curved (form space p = 4.09, .002; shape space p = 12.82, .002). These features of mice lacking sclerostin largely correspond to the changes of the facial skeleton observed in sclerosteosis. This alignment further supports claims that the Sost gene plays a fundamental role in bony facial development in rodents and humans alike.

Caspase inhibitor attenuates the shape changes in the alveolar ridge following tooth extraction: A pilot study in rats

“…This type of analysis has also been used in dentistry, including orthodontics 18‐20 and craniofacial surgery 21 . In addition, we have recently proposed the use of geometrics morphometrics to characterize skull deformation in sclerostin knockout mice 11 . Here, geometric morphometrics revealed that caspase inhibitors limited the deformation of the lingual alveolar ridge following M1 tooth extraction.…”

“…Protocols, handling, and care of the mice conformed to the Austrian federal law for animal protection. Sample size calculation was based on a previous study 11 . In brief, we expected a 15% effect of the difference between the groups.…”

“…Tests and graphics were performed using graphpad prism version 8.3.15. Owing to the pilot nature of the study, the sample size was chosen based on experience from previous studies 11 to balance the ability to measure significant differences while reducing the number of animals used. Significance was set at P < .05.…”

“…Sample size calculation was based on a previous study. 11 In brief, we expected a 15% effect of the difference between the groups. Considering a power 80%, a type I error rate of 5%, and six degrees of freedom, seven rats per group were necessary and one extra rat per group was added in the event of an euthanasia was performed on day 11 and with an overdose of pentobarbital (300 mg/kg i.c.…”

Effects of Multi-Generational Soft Diet Consumption on Mouse Craniofacial Morphology

“…Lastly, we calculated the centroid size (the square root of the sum of squared Euclidean distances from each landmark to their own centroid) for the cranium and mandible. Generally, this measurement is the standard for assessing size in GMA (Le and Kume, 2000;Schwarze et al, 2019).…”