Masticatory muscle morphology in early postnatal mice with osteogenesis imperfecta

Abstract

Purpose: Osteogenesis imperfecta (OI) is a connective tissue disorder resulting from mutations in COL1A1 or COL1A2, responsible for encoding type I collagen alpha chains. While OI is primarily distinguished by manifestations of bone fragility, including recurrent fractures and bone deformities, muscle abnormalities have also been documented in those affected by OI. While prior research has shown postcranial muscle weakness in mouse models of OI, it remains unclear whether this also applies to feeding musculature and if these differences are present at birth or develop postnatally. This study investigates the development of the masticatory muscles during the early postnatal period in a mouse model. Our hypothesis posits that mice affected by OI will exhibit decreased muscle mass, and therefore potentially weaker muscles, in comparison to unaffected mice.

Methods: Cranial tissues from OIM mice (B6C3Fe a/a-Col1a2oim/J) and unaffected wild type (WT) littermates were collected at day of birth (P0) and postnatal day 14 (P14). Tissues were fixed and stained with 1.25% buffered Lugol’s solution, then micro-CT scanned with a reconstruction of 0.02 mm3 voxels. 3D Slicer software was used to isolate and measure the volumes of the superficial masseter, deep masseter, and temporalis muscles. Muscle volumes were compared between genotypes using a Mann-Whitney U test.

Results: At birth, no significant differences were observed in body mass or muscle volumes between OIM and WT mice. A trend was observed for OIM mice to have lower superficial masseter volumes compared to WT mice at P0, but this difference was not significant. At P14, OIM mice have significantly lower body weights (p=0.002). Data collection is ongoing for volumetric muscle data from the P14 stage. After birth, body masses diverge rapidly between OIM and WT mice. These growth curves suggest poor feeding performance during the suckling stage in OIM mice. Although masticatory muscle volumes (similar to body mass) start out similar between genotypes at birth, a trend for decreased superficial masseter volume in OIM mice suggests feeding musculature will also lag behind unaffected mice during early postnatal growth.

Conclusion: The production of strain above an osteogenic threshold by feeding musculature is critical to typical craniofacial growth during early life. Weaker masticatory muscles may produce lower (yet still osteogenic) levels of strain, contributing to the midfacial hypoplasia seen in OIM mice. A better understanding of muscle development during this critical growth period will provide insight on feeding disorders seen in OI, and the development of the craniofacial phenotype in pediatric patients with OI.

Description

Keywords

Citation

Rights

License