Related Experiment Videos
Morphological and biochemical studies of a mouse mutant (fro/fro) with bone fragility
M P Muriel1, J Bonaventure, R Stanescu
1URA 584 CNRS, Clinique Maurice Lamy, Hôpital des Enfants-Malades, Paris, France.
Abstract:
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.
Insights
The fragilitas ossium (fro) mouse mutation causes bone fragility similar to human osteogenesis imperfecta. This mouse model shows reduced osteonectin and bone sialoprotein, not collagen defects, offering insights into non-collagenous bone disorders.
Area of Science:
- Genetics
- Developmental Biology
- Biochemistry
Background:
- The fragilitas ossium (fro) mutation was identified in mice exposed to a chemical mutagen.
- Affected mice exhibit skeletal deformities resembling human osteogenesis imperfecta.
- Initial investigations ruled out defects in type I and V collagen synthesis or structure.
Purpose of the Study:
- To investigate the molecular basis of the fragilitas ossium (fro) mutation in mice.
- To determine if the observed bone fragility is linked to collagen abnormalities.
- To explore potential alterations in non-collagenous bone matrix proteins.
Main Methods:
- Radiological and histological analysis of affected mice.
- Biochemical assays of collagen synthesis and characterization in fibroblasts.
- Quantification of bone mineral content (ash).
- Analysis of specific bone matrix proteins (osteonectin, bone sialoprotein) and their mRNA levels.
Main Results:
- Mice with the fro mutation displayed reduced long bone ash content and skeletal deformities.
- No defects were found in type I and V collagen synthesis, secretion, or peptide structure.
- A significant decrease in bone osteonectin (30%) and bone sialoprotein (5%) was observed.
- Osteonectin mRNA levels in fibroblasts were reduced by approximately 50% in fro/fro mice.
Conclusions:
- The fragilitas ossium (fro) mutation in mice leads to bone fragility without detectable collagen abnormalities.
- Reduced levels of osteonectin and bone sialoprotein are associated with the fro mutation.
- The fro/fro mouse serves as a valuable model for studying human bone fragility conditions not caused by collagen defects.
- Further research is needed to elucidate the exact cause of defective osteonectin expression in this model.