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Alterations in mandibular morphology associated with glypican 1 and glypican 3 gene mutations
Author(s) -
Mian M.,
Ranjitkar S.,
Townsend G. C.,
Anderson P. J.
Publication year - 2017
Publication title -
orthodontics and craniofacial research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.664
H-Index - 55
eISSN - 1601-6343
pISSN - 1601-6335
DOI - 10.1111/ocr.12170
Subject(s) - knockout mouse , gene knockout , biology , morphology (biology) , population , gene , genetics , medicine , environmental health
Structured Abstract Objectives Glypican 1 ( GPC 1) and glypican 3 ( GPC 3) are bone co‐regulators that act downstream in many of the signalling pathways associated with craniosynostosis. Morphometric data from GPC ‐knockout mice were analysed to determine whether elimination of GPC 1 and GPC 3 genes would alter mandibular morphology. Setting and sample population The murine model included five male and five female mandibles in each of GPC 1‐knockout, GPC 1/ GPC 3‐knockout and wild‐type (control) groups. Female GPC 3‐knockout mice had a very high rate of perinatal lethality, and therefore, only five males were included in this group. Methods The mandibular morphology of GPC 1‐knockout (n=10), GPC 3‐knockout (n=5), GPC 1/ GPC 3‐knockout (n=10) and wild‐type (n=10) mice was compared by analysing five landmark‐based linear dimensions: anterior and posterior lengths, as well as ascending, descending and posterior heights. Measurements were recorded on three‐dimensional micro‐ CT reconstructions. Results GPC 3‐knockout mandibles were larger than wild‐type mandibles for all dimensions ( P <.05). Mandibular heights were more affected than lengths. A decreasing trend of mandibular dimensions across the mouse groups ( GPC 3‐knockout> GPC 1/ GPC 3‐knockout> GPC 1‐knockout=wild‐type) ( P <.05) indicated that an increase in mandibular size was associated with increased GPC 3 expression, but not GPC 1. Conclusions Alterations in GPC 3 expression are likely to mediate changes to mandibular size in craniosynostosis. These findings have potential future applications in the prevention and treatment of craniosynostosis and associated craniofacial dysmorphology.