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    Genetic Susceptibility to Intervertebral Disc Degeneration in Transgenic Mice

    The etiology of most of the degenerative changes in the spine continues to remain obscure. However, several lines of evidence suggest that genetic factors may play an important role in the onset of degenerative changes, in addition to various environmental factors. We have generated transgenic mice expressing mutant αl(IX) collagen in the cartilage matrix. They developed progressive intervertebral disc degeneration with age as well as joint degeneration. Both radiologic and histologic studies indicated that cervical and lumbar disc degeneration was more advanced in the transgenic mice than in control littermates. The initial degenerative changes included shrinkage and replacement of the nucleus pulposus with consolidated fibrous tissue, that resulted in a loss of nuclear-anular demarcation. Partial disruption in the lamellar structure of the anulus fibrosus also occurred at this stage. With age, the disc degeneration progressively advanced and sometimes caused herniation of disc material and mild osteophyte formation. These findings imply that genetic abnormalities of cartilage matrix components, such as type IX collagen, may be responsible for certain degenerative diseases in the spine.