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Alterations in mandibular morphology associated with glypican 1 and glypican 3 gene mutations
M Mian1, S Ranjitkar1, G C Townsend1
1Adelaide Dental School, The University of Adelaide, Adelaide, SA, Australia.
Objectives:
Glypican 1 (GPC1) and glypican 3 (GPC3) 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 GPC1 and GPC3 genes would alter mandibular morphology.
Setting And Sample Population:
The murine model included five male and five female mandibles in each of GPC1-knockout, GPC1/GPC3-knockout and wild-type (control) groups. Female GPC3-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 GPC1-knockout (n=10), GPC3-knockout (n=5), GPC1/GPC3-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:
GPC3-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 (GPC3-knockout>GPC1/GPC3-knockout>GPC1-knockout=wild-type) (P<.05) indicated that an increase in mandibular size was associated with increased GPC3 expression, but not GPC1.
Conclusions:
Alterations in GPC3 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.
