HALLGRIMSSON, Benedikt; BROWN, Jevon J.Y.; FORD-HTCHINSON, Alice F.; JIRIK, Frank R.; University of Calgary; University of Calgary; University of Calgary; University of Calgary: CANALIZATION AND MORPHOLOGICAL INTEGRATION OF CRANIOFACIAL MORPHOLOGY IN BRACHYMORPH MICE AS ASSESSED BY COMPUTED MICROTOMOGRAPHY

Although it is well recognized that many different mutations potentially influence phenotypic variability as well as the mean, the underlying mechanisms for variability effects are very poorly understood. The brachymorph (bm) mutant mouse phenotype results from an autosomal recessive mutation in the phosphoadenosine-phosphosulfate synthase 2 gene (PAPSS2). The major cranial manifestation of bm/bm mice is the dramatic reduction in the growth of the chondrocranium which stems from the undersulfation of cartilage matrix glycosaminoglycans (GAGs). We found that the reduction in the growth of the chondrocranium in bm/bm mice was associated with an altered pattern of craniofacial shape variation, a significant increase in phenotype variance, and a dramatic increase in morphological integration for craniofacial shape. Both effects were the greatest in the basicranium. The altered variation pattern indicated that the mutation produces developmental influences on shape that were not present in the wildtype controls. Since the mutation dramatically reduces sulfation of GAGs, we infer that this influence is due to variation among individuals with respect to the degree of sulfation, or variable expressivity of the mutation. This variation may be due to variation at other loci that influence the extent of sulfation, environmental effects, or intrinsic effects. We infer that chondrocranial development exhibits greater sensitivity to variation in the sulfation of GAGs when levels of sulfation is low. In the physiological range, levels of sulfation probably contribute minimally to phenotypic variation. This case illustrates canalization in a particular developmental context.