Absolute and Relative Morphometric Differences in the Craniofacial Skeleton of OIM−/− Mice and Wild‐Type Littermates

Abstract

Osteogenesis imperfecta (OI) is a genetic disorder of type 1 collagen (Col1) that is characterized by increased skeletal fragility, low bone mineral density, and shortened stature. Compared to the postcranial phenotype associated with OI, relatively little is known about the etiology of the craniofacial phenotype or its presentation in experimental models. In general, humans with the severe OI type III are reported to exhibit midfacial hypoplasia (“triangle face”), basicranial shortening with relative macrocephaly, and dental malocclusions. Similar reductions in craniofacial dimensions have been documented in rodent models with induced Col1 defects. Here we use a mouse model of OI type III in order to investigate the influence of Col1 on the growth and scaling of the craniofacial skeleton.The homozygous OI murine (OIM−/−) is a mouse strain with a nonlethal recessively inherited mutation of the COL1A2 gene. Wild‐type (WT) and OIM−/− littermates were weaned at 21d and raised until adult (16 weeks). 3D morphometric landmarks were collected from serial in‐vivo μCT scans at 4, 10, and 16 weeks using etdips software. Interlandmark distances (ILDs) and centroid sizes were calculated using Past 2.17 software. ILDS were scaled against skull/mandible centroid size and skull/mandible length to account for the effect of size. ANCOVAs and Kruskal‐Wallis ANOVAs were used to compare centroid sizes and both absolute and relative (scaled) morphometric distances between the genotypes.When comparing absolute morphometric distances, adult OIM−/− mice have shorter skulls, anterior basicrania, palates, mandibles, and both mandibular and maxillary toothrows. However, OIM−/− mice are smaller overall than their WT littermates as measured by both body mass and craniomandibular centroid sizes. When the effects of size are accounted for, the trend for interlandmark distances in WT mice to be greater than those in OIM−/− mice is significantly reduced or even reversed. For example, when scaled to centroid size, no significant difference exists between WT and OIM−/− mice in skull, basicranial, or mandibular length. OIM−/− mice have a short midface, short nasal bones, tall mandibular corpora and long mandibular toothrows for their size.These findings underscore the importance of size and scaling in morphometric analyses. The deleterious effect of Col1 mutations on global skeletal dimensions, in combination with localized morphometric changes, may underlie the facial phenotype seen in human patients with OI type III. Attempts to identify these localized changes should first account for the restricted growth and small body sizes present in individuals with OI.Support or Funding InformationThis research was supported by an Indiana University Collaborative Research Grant and the Ralph W. and Grace Showalter Trust.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.