Masticatory musculature does not increase intracranial volume in myostatin-knockout mice

Objectives: Stedman et al., (2004) suggested that a mutation in the myosin heavy chain gene (MYH 16) may have indirectly increased brain size in human evolution by reducing masticatory muscle size, decreasing its subsequent compressive effects on cranial vault growth, and thus removing a constraint on greater encephalization. If masticatory muscle size were increased, then a reduction in brain growth should also occur. The present study was designed to test this hypothesis using a Myostatin (GDF-8) knockout mouse model. Myostatin is a negative regulator of skeletal muscle growth, and individuals lacking this gene show significant hypermuscularity.

Methods: Fourteen (8 wild-type and 7 GDF-8 -/- knockout), 1 day old and 16 (9 wild-type and 7 GDF-8 -/- knockout), 180 day old male CD-1 mice were used. Body and masseter muscle weights were obtained. Standardized lateral and dorsoventral radiographs were taken of each skull. Cephalometric landmarks were identified on the radiographs and intracranial volume (cranial vault length*width*height) was calculated. Mean differences were assessed using a two-way ANOVA.

Results: Myostatin knock-out mice had significantly greater body (F=7.9;p<0.01) and masseter muscle weights (F=22.35;p<0.001) compared to wild-type controls by 180 days. No significant differences (F=2.38;ns) in intracranial volume were noted between myostatin knock-out mice and wild-type controls. Muscle weight was not significantly correlated with intracranial volume in 1 or 180 day old mice.

Conclusion: Results from this murine model demonstrate that hypermuscularity of the masticatory musculature did not reduce intracranial volume. In contrast, there is abundant data demonstrating just the opposite, that brain growth determines cranial vault growth and morphology and that the masticatory apparatus only affects ectocranial morphology. Results do not support the Stedman et al., (2004) hypothesis that a reduction in masticatory musclature relaxed compressive forces on the cranial vault and allowed the brain to grow bigger. Alternative hypotheses should still be explored.