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 activation and its expression in developing tissues such as developing bone and muscle. To test the functional role of tetranectin directly, we have generated mice with a targeted disruption of the gene. We report that the tetranectin-deficient mice exhibit kyphosis, a type of spinal deformity characterized by an increased curvature of the thoracic spine. The kyphotic angles were measured on radiographs. In 6-month-old normal mice (n = 27), the thoracic angle was 73 degrees +/- 2 degrees, while in tetranectin-deficient 6-month-old mice (n = 35), it was 93 degrees +/- 2 degrees (P < 0.0001). In approximately one-third of the mutant mice, X-ray analysis revealed structural changes in the morphology of the vertebrae. Histological analysis of the spines of these mice revealed an apparently asymmetric development of the growth plate and of the intervertebral disks of the vertebrae. In the most advanced cases, the growth plates appeared disorganized and irregular, with the disk material protruding through the growth plate. Tetranectin-null mice had a normal peak bone mass density and were not more susceptible to ovariectomy-induced osteoporosis than were their littermates as determined by dual-emission X-ray absorptiometry scanning. These results demonstrate that tetranectin plays a role in tissue growth and remodeling. The tetranectin-deficient mouse is the first mouse model that resembles common human kyphotic disorders, which affect up to 8% of the population.
Iba
K
K
The Institute of Molecular Pathology, University of Copenhagen, Copenhagen, Denmark.
Durkin
M E
ME
Johnsen
L
L
Hunziker
E
E
Damgaard-Pedersen
K
K
Zhang
H
H
Engvall
E
E
Albrechtsen
R
R
Wewer
U M
UM
D000818:Animals; D001798:Blood Proteins / Q000235:genetics / Q000502:physiology*; D015519:Bone Density; D004198:Disease Susceptibility; D005260:Female; D017353:Gene Deletion; D018390:Gene Targeting / Q000379:methods; D007738:Kyphosis / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D037102:Lectins / Q000235:genetics / Q000502:physiology*; D037181:Lectins, C-Type; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010024:Osteoporosis / Q000209:etiology; D010052:Ovariectomy; D013904:Thoracic Vertebrae / Q000002:abnormalities / Q000473:pathology
D001798:Blood Proteins; D037102:Lectins; D037181:Lectins, C-Type; C048648:tetranectin