title: Craniofacial variability and morphological integration in mice susceptible to cleft lip and palate.
abstract: A/WySnJ mice are an inbred strain that develops cleft lip with or without cleft palate (CL/P) with a frequency of 25-30% and a predominantly unilateral expression pattern. As in humans, the pattern of incomplete penetrance, and variable and frequent unilateral expression suggests a role for altered regulation of variability (developmental stability, canalization and developmental integration) during growth. We compared both mean and variability parameters for craniofacial shape and size among A/WySnJ mice, a strain that does not develop CL/P (C57BL/6J) and their F1 cross. We show that adult A/WySnJ mice that do not express cleft lip exhibit decreased morphological integration of the cranium and that the co-ordination of overall shape and size variation is disrupted compared with both C57BL/6J mice and the F1 cross. The decrease in integration is most pronounced in the palate and face. The absence of this pattern in the F1 cross suggests that it is determined by recessive genetic factors. By contrast, the shape differences between the strains, which are thought to predispose A/WySnJ mice to CL/P, show a range of dominance which suggests a polygenic basis. We suggest that decreased integration of craniofacial growth may be an aetiological factor for CL/P in A/WySnJ mice.
authors.affiliation: Department of Cell Biology & Anatomy, the Joint Injury and Arthritis Research Group, University of Calgary, Canada. bhallgri@ucalgary.ca
authors.forename: Benedikt
authors.initials: B
authors.lastname: Hallgrímsson
authors.forename: Curtis J
authors.initials: CJ
authors.lastname: Dorval
authors.forename: Miriam Leah
authors.initials: ML
authors.lastname: Zelditch
authors.forename: Rebecca Z
authors.initials: RZ
authors.lastname: German
mesh_terms: D000818:Animals; D002971:Cleft Lip / Q000196:embryology / Q000235:genetics; D002972:Cleft Palate / Q000196:embryology / Q000235:genetics; D019465:Craniofacial Abnormalities / Q000196:embryology / Q000235:genetics*; D047108:Embryonic Development; D005147:Facial Bones / Q000196:embryology; D020022:Genetic Predisposition to Disease; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D013045:Species Specificity