Morphological and biochemical studies of a mouse mutant (fro/fro) with bone fragility.
The mutation fragilitas ossium (fro) was discovered in a random-bred stock of mice during an experiment aimed at detecting recessive lethal mutations after treatment of the postmeiotic germ cells of male mice with tris (1-aziridinyl)phosphine sulphide. The affected mice were moderately runted and had deformities in all four limbs. The radiological and histological findings indicate that the mutant is similar to human osteogenesis imperfecta. The ash content of long bones was lower in the mutant. A defect of type I collagen could not be detected. The electrophoretic patterns of alpha bands of type I and V collagen and CB derived peptides of type I collagen from bone and skin showed no abnormalities. The total collagen synthesis and secretion in cultures of dermal fibroblasts, as well as the gel electrophoresis of procollagen and collagen chains synthesized, and of their CB peptides, were the same as those found in the controls. The percentage of type I and type V collagen synthesized was similar; that of type III was lower in the mutants. Bone osteonectin was found to be decreased by 30% and bone sialoprotein by 5%. The mRNA level for osteonectin was decreased in the fibroblasts of the mutant by about 50%. Whether the defective expression of the osteonectin in fro/fro mice is due to a mutation in the gene itself or its regulatory site(s), or is secondary to other factors remains to be established. The fro/fro mouse may represent a model for some forms of human bone fragility without collagen abnormalities.
Muriel
M P
MP
URA 584 CNRS, Clinique Maurice Lamy, Hôpital des Enfants-Malades, Paris, France.
Bonaventure
J
J
Stanescu
R
R
Maroteaux
P
P
Guénet
J L
JL
Stanescu
V
V
D000818:Animals; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000378:metabolism; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D005808:Genes, Recessive / Q000235:genetics; D006651:Histocytochemistry; D051379:Mice; D008817:Mice, Mutant Strains; D008903:Minerals / Q000378:metabolism; D010013:Osteogenesis Imperfecta / Q000000981:diagnostic imaging / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D015676:Osteonectin / Q000235:genetics / Q000378:metabolism; D011347:Procollagen / Q000032:analysis; D011506:Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011859:Radiography; D012867:Skin / Q000166:cytology / Q000473:pathology
D008903:Minerals; D015676:Osteonectin; D011347:Procollagen; D011506:Proteins; D012333:RNA, Messenger; D003094:Collagen