Targeted disruption of Mig-6 in the mouse genome leads to early onset degenerative joint disease

AUTOR(ES)

Zhang, Yu-Wen

FONTE

National Academy of Sciences

RESUMO

Degenerative joint disease, also known as osteoarthritis, is the most common joint disorder in human beings. The molecular mechanism underlying this disease is not fully understood. Here, we report that disruption of mitogen-inducible gene 6 (Mig-6) in mice by homologous recombination leads to early onset degenerative joint disease, which is revealed by simultaneous enlargement and deformity of multiple joints, degradation of articular cartilage, and the development of bony outgrowths or osteophyte formation within joint space. The osteophyte formation appears to be derived from proliferation of mesenchymal progenitor cells followed by differentiation into chondrocytes. Absence of the Rag2 gene does not rescue the joint phenotype, excluding a role for the acquired immune system in the development of this disease. Our results provide insight into the mechanism of osteoarthritis by showing that loss of Mig-6 leads to early onset of this disease, implying that this gene or its pathway is important in normal joint maintenance. Because of the striking similarity of osteoarthritis in humans and mice, the Mig-6 mutant mouse should provide a useful animal model for studying the mechanism of this disease and for testing drugs or therapies for treating osteoarthritis.

Documentos Relacionados

• Targeted disruption of the mouse Stat3 gene leads to early embryonic lethality
• Targeted disruption of mouse centromere protein C gene leads to mitotic disarray and early embryo death
• The Biology of Degenerative Joint Disease
• Targeted Disruption of the Ceacam1 (MHVR) Gene Leads to Reduced Susceptibility of Mice to Mouse Hepatitis Virus Infection
• Mig-6 is required for appropriate lung development and to ensure normal adult lung homeostasis