Table 1.
The gene–disease/trait association and bone-related phenotypes of the gene-deficient mice of the five candidate genes
| Gene | Gene–disease/trait association in humans | Bone-related phenotypes of target-gene-deficient mice |
|---|---|---|
| FLNB | Boomerang dysplasia [16] | Smaller body size, reduced body weight, “hourglass” body shape, restricted upper body movement, and aberrant mineralization in the neural arches leading to fusion of individual vertebrae [22] |
| Larson syndrome [17, 18] | ||
| Spondylocarpotarsal synostosis [18, 19] | ||
| Atelosteogenesis I and III [18, 20] | Kyphotic and scoliotic malformations of the vertebral column, reduced body weight, shorter bones, reduced BMD in the middiaphyseal area of tibiae, reduced cortical thickness, reduction in hyaline cartilage in the ribs, metacarpal bones, phalanges, and tarsal bones [23] | |
| BMD [21] | ||
| PPARG | Serum osteoprotegerin level [24, 25] | PPARG+/− mice exhibit high bone mass compared with wild-type mice. The difference in bone volume between the mice of two genotypes becomes more prominent at 52 weeks [27] |
| Total body BMD [26] | ||
| PTHR1 | Femoral neck BMD [28–31] | No abnormal bone-related phenotypes were reported in PTHR1-deficient mice |
| Eiken syndrome [32] | ||
| Blomstrand chondrodysplasia [32, 33] | ||
| CRTAP | Osteogenesis imperfecta [34–37] | Shortening of long bone segments (particularly the proximal segment of the limb), decreased bone volume/tissue volume ratio, decreased trabecular thickness, decreased trabecular number, increased trabecular separation, reduced bone formation rate due to a reduction in the mineral apposition rate, and decreased mineralization lag time [35] |
| TDGF1 | Ranked first in the prediction of osteoporosis candidate genes within the 3p14-25 [38] | No abnormal bone-related phenotypes were reported in TDGF1-deficient mice |