title: The brachymorph mouse and the developmental-genetic basis for canalization and morphological integration.
abstract: Although it is well known that many mutations influence phenotypic variability as well as the mean, the underlying mechanisms for variability effects are very poorly understood. The brachymorph (bm) phenotype results from an autosomal recessive mutation in the phosphoadenosine-phosphosulfate synthetase 2 gene (Papps2). A major cranial manifestation is a dramatic reduction in the growth of the chondrocranium which results from undersulfation of glycosaminoglycans (GAGs) in the cartilage matrix. We found that this reduction in the growth of the chondrocranium is associated with an altered pattern of craniofacial shape variation, a significant increase in phenotypic variance and a dramatic increase in morphological integration for craniofacial shape. Both effects are largest in the basicranium. The altered variation pattern indicates that the mutation produces developmental influences on shape that are not present in the wildtype. As the mutation dramatically reduces sulfation of GAGs, we infer that this influence is variation among individuals in the degree of sulfation, or variable expressivity of the mutation. This variation may be because of genetic variation at other loci that influence sulfation, environmental effects, or intrinsic effects. We infer that chondrocranial development exhibits greater sensitivity to variation in the sulfation of chondroitin sulfate when the degree of sulfation is low. At normal levels, sulfation probably contributes minimally to phenotypic variation. This case illustrates canalization in a particular developmental-genetic context.
authors.affiliation: Department of Cell Biology & Anatomy and the Joint Injury and Arthritis Research Group, University of Calgary, 3330 Hospital Dr., Calgary, AB, Canada T2N 4N1. bhallgri@ucalgary.edu
authors.forename: Benedikt
authors.initials: B
authors.lastname: Hallgrímsson
authors.forename: Jevon J Y
authors.initials: JJ
authors.lastname: Brown
authors.forename: Alice F
authors.initials: AF
authors.lastname: Ford-Hutchinson
authors.forename: H David
authors.initials: HD
authors.lastname: Sheets
authors.forename: Miriam L
authors.initials: ML
authors.lastname: Zelditch
authors.forename: Frank R
authors.initials: FR
authors.lastname: Jirik
mesh_terms: D000717:Anatomy, Comparative; D000818:Animals; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D014644:Genetic Variation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009024:Morphogenesis; D009097:Multienzyme Complexes / Q000235:genetics*; D009154:Mutation; D010641:Phenotype; D012886:Skull / Q000033:anatomy & histology / Q000254:growth & development*; D013430:Sulfate Adenylyltransferase / Q000235:genetics*
chemical_list: D009097:Multienzyme Complexes; C022322:PAPS synthetase; D013430:Sulfate Adenylyltransferase