title: Age-related changes in craniofacial morphology in GDF-8 (myostatin)-deficient mice.
abstract: It is well recognized that masticatory muscle function helps determine morphology, although the extent of function on final form is still debated. GDF-8 (myostatin), a transcription factor is a negative regulator of skeletal muscle growth. A recent study has shown that mice homozygous for the myostatin mutation had increased muscle mass and craniofacial dysmorphology in adulthood. However, it is unclear whether such dysmorphology is present at birth. This study examines the onset and relationship between hypermuscularity and craniofacial morphology in neonatal and adult mice with GDF-8 deficiency. Fifteen (8 wild-type and 7 GDF-8 -/-), 1-day-old and 16 (9 wt and 7 GDF-8 -/-), 180-day-old male CD-1 mice were used. Standardized radiographs were taken of each head, scanned, traced, and cephalometric landmarks identified. Significant mean differences were assessed using a group x age, two-way ANOVA. Myostatin-deficient mice had significantly (P < 0.01) smaller body and masseter muscle weights and craniofacial skeletons at 1 day of age and significantly greater body and masseter muscle weights at 180 days of age compared to controls. Myostatin-deficient mice showed significantly (P < 0.001) longer and "rocker-shaped" mandibles and shorter and wider crania compared to controls at 180 days. Significant correlations were noted between masseter muscle weight and all cephalometric measurements in 180-day-old Myostatin-deficient mice. Results suggest that in this mouse model, there may be both early systemic skeletal growth deficiencies and later compensatory changes from hypermuscularity. These findings reiterate the role that masticatory muscle function plays on the ontogeny of the cranial vault, base, and most notably the mandible.
authors.affiliation: Pittsburgh Cleft-Craniofacial Research Center, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Vecchione
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Miller
authors.forename: Craig
authors.initials: C
authors.lastname: Byron
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Cooper
authors.forename: Timothy
authors.initials: T
authors.lastname: Barbano
authors.forename: James
authors.initials: J
authors.lastname: Cray
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Losee
authors.forename: Mark W
authors.initials: MW
authors.lastname: Hamrick
authors.forename: James J
authors.initials: JJ
authors.lastname: Sciote
authors.forename: Mark P
authors.initials: MP
authors.lastname: Mooney
mesh_terms: D000367:Age Factors; D000818:Animals; D002508:Cephalometry; D019465:Craniofacial Abnormalities / Q000209:etiology / Q000473:pathology*; D008297:Male; D008406:Masseter Muscle / Q000254:growth & development / Q000473:pathology*; D008445:Maxillofacial Development; D051379:Mice; D018345:Mice, Knockout; D024510:Muscle Development; D055435:Myostatin / Q000502:physiology*; D009929:Organ Size
chemical_list: C525912:Mstn protein, mouse; D055435:Myostatin