Mice with a targeted deletion of the tetranectin gene exhibit a spinal deformity

Tetranectin is a plasminogen-binding, homotrimeric protein belonging to the C-type lectin family of proteins. Tetranectin has been suggested to play a role in tissue remodeling, due to its ability to stimulate plasminogen act ivation and its expression in developing tissues such as developing bone an d muscle. To test the functional role of tetranectin directly, we have gene rated mice with a targeted disruption of the gene. We report that the tetra nectin-deficient mice exhibit kyphosis, a type of spinal deformity characte rized by an increased curvature of the thoracic spine. The kyphotic angles were measured on radiographs. In 6-month-old normal mice (n = 27), the thor acic angle was 73 degrees +/- 2 degrees, while in tetranectin-deficient 6-m onth-old mice (n = 35), it was 93 degrees +/- 2 degrees (P < 0.0001). In ap proximately one-third of the mutant mice, X-ray analysis revealed structura l changes in the morphology of the vertebrae. Histological analysis of the spines of these mice revealed an apparently asymmetric development of the g rowth plate and of the intervertebral disks of the vertebrae. In the most a dvanced cases, the growth plates appeared disorganized and irregular, with the disk material protruding through the growth plate. Tetranectin-null mic e had a normal peak bone mass density and were not more susceptible to ovar iectomy-induced osteoporosis than were their littermates as determined by d ual-emission X-ray absorptiometry scanning. These results demonstrate that tetranectin plays a role in tissue growth and remodeling. The tetranectin-d eficient mouse is the first mouse model that resembles common human kyphoti c disorders, which affect up to 8% of the population.