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Allele Symbol Allele Name Allele ID |
Ctsktm1(cre)Ska targeted mutation 1, Shigeaki Kato MGI:3764465 |
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| Summary |
8 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• females mice have 1.5 times more osteoclasts on bone surface compared to wild-type females
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• osteoclasts are resistant to estrogen induced apoptosis due to a failure to produce fas-ligand
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• females, but not males, have decreased density of the femur
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• 12 week old female but not male mice have 1.6 fold loss of trabecular bone volume that is indicative of osteoporosis
• loss of bone volume is not increased upon ovariectomy
• treatment with estrogen fails to rescue the bone loss
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• increased mineral apposition rate in female mice
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• increased bone formation rate in female mice
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• females have increased rates of bone resorption as measured by eroded surface per bone surface
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• females mice have 1.5 times more osteoclasts on bone surface compared to wild-type females
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• osteoclasts are resistant to estrogen induced apoptosis due to a failure to produce fas-ligand
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• females mice have 1.5 times more osteoclasts on bone surface compared to wild-type females
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• osteoclasts are resistant to estrogen induced apoptosis due to a failure to produce fas-ligand
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
3-week-old Ctsktm1(cre)Ska/Ctsktm1(cre)Ska Snx10tm1c(EUCOMM)Raba/Snx10tm1c(EUCOMM)Raba mice are growth retarded, have a tooth eruption defect, and are osteopetrotic
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• by 3 weeks of age, mice exhibit mild growth retardation
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• osteoclast precursors cultured in vitro show impaired extracellular acidification capacity, have impaired endocytosis, and only form rudimentary ruffled borders
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• 9 week old bones show a 30% increase in bone mineral density
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• smaller bone volume/tissue volume ratio
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• long bones exhibit marrow cavities filled with unresorbed bone and presence of mineralized trabeculae within the bone marrow space, however trabeculae are not covered by thick layers of unmineralized osteoid
• however, a moth-eaten bone appearance is not seen, osteoid volume per bone volume is normal, and mice are not rachitic
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• growth plate thickness is smaller
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• osteoclast precursors cultured in vitro show impaired extracellular acidification capacity, have impaired endocytosis, and only form rudimentary ruffled borders
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• osteoclast precursors cultured in vitro show impaired extracellular acidification capacity, have impaired endocytosis, and only form rudimentary ruffled borders
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| N |
• mice show normal gastric pH, serum calcium levels and parathyroid hormone levels
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Low bone mass in Cthrc1tm1.1Suna/Cthrc1tm1.1Suna Ctsktm1(cre)Ska/Ctsk+ mice
| N |
• mice exhibit normal bone resorption parameters
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• however, RANKL injection restores bone mass
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• decreased osteoid surface
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• decreased bone formation rate
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice exhibit normal bone formation
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• impaired
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• impaired
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• impaired
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• impaired
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• osteoclasts grown on plastic dishes or bovine cortical bone slices exhibit altered morphology with tartrate-resistant acid phosphatase (TRAP) staining clustered in the perinuclear area
• osteoclasts cultured on bone show barely detectable localization of LAMP-2 positive lysosomes at the ruffled border and CTSK (cathepsin K) secretion in the resorption lacuna, while the sealing zone appears intact, indicating defects in lysosome peripheral distribution and ruffled border formation
• osteoclasts cultured on glass have lysosomes clustered at the perinuclear region as opposed to the cell periphery
• in vitro osteoclast differentiation and the cytoskeletal organization of actin and microtubules are relatively normal in osteoclasts cultured on glass and bone
• in vivo, osteoclast number and surface are similar to those in control mice
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• in vitro, the bone resorption capacity of osteoclasts cultured on bone slices is markedly decreased, as shown by resorption pit staining and the amount of CTx-I (a bone resorption marker) released in the culture medium
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• at 2 months of age, both sexes exhibit a >60% increase in trabecular bone volume to tissue volume (BV/TV) in long bones and vertebrae
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• at 2 months of age, osteoblast number and surface are slightly decreased, as shown by histomorphometry analysis of femurs
• however, in vitro differentiation of osteoblasts derived from either calvaria or bone marrow stromal cells is normal
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• mice show an increased trabecular number, as measured by micro-CT
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• mice show decreased trabecular separation, as measured by micro-CT
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• at 2 months of age, both sexes exhibit a >60% increase in trabecular bone mass in long bones and vertebrae relative to control mice; increased trabecular bone mass persists until 5 months of age
• however, no overt defects are detected in other tissues or organs
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• at 2 months of age, femoral bone mineral apposition rate is lower than that in control mice
• however, in vitro bone matrix deposition is normal
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• at 2 months of age, femoral bone formation rate is lower than that in control mice
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• in vitro, the bone resorption capacity of osteoclasts cultured on bone slices is markedly decreased, as shown by resorption pit staining and the amount of CTx-I (a bone resorption marker) released in the culture medium
• reduced bone resorption capacity of osteoclasts is caused by defects in the peripheral positioning and secretion of lysosomes rather than defects in cytoskeletal organization
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• cultured osteoclasts show defects in lysosome peripheral distribution and ruffled border formation
• mouse embryonic fibroblasts (MEFs) exhibit a slightly increased number of LAMP-2 positive lysosomes around nuclei
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• osteoclasts cultured on bone slices show barely detectable secretion of cathepsin K (CTSK, the major lysosomal acidic hydrolase in osteoclasts) in the resorption lacuna beneath the ruffled border
• Ca2+-regulated exocytosis of lysosomes is significantly inhibited, as determined by the release of the lysosomal enzyme beta-hexoaminidase in streptolysin-O permeabilized MEFs
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• osteoclasts grown on plastic dishes or bovine cortical bone slices exhibit altered morphology with tartrate-resistant acid phosphatase (TRAP) staining clustered in the perinuclear area
• osteoclasts cultured on bone show barely detectable localization of LAMP-2 positive lysosomes at the ruffled border and CTSK (cathepsin K) secretion in the resorption lacuna, while the sealing zone appears intact, indicating defects in lysosome peripheral distribution and ruffled border formation
• osteoclasts cultured on glass have lysosomes clustered at the perinuclear region as opposed to the cell periphery
• in vitro osteoclast differentiation and the cytoskeletal organization of actin and microtubules are relatively normal in osteoclasts cultured on glass and bone
• in vivo, osteoclast number and surface are similar to those in control mice
|
|
• in vitro, the bone resorption capacity of osteoclasts cultured on bone slices is markedly decreased, as shown by resorption pit staining and the amount of CTx-I (a bone resorption marker) released in the culture medium
|
|
• osteoclasts grown on plastic dishes or bovine cortical bone slices exhibit altered morphology with tartrate-resistant acid phosphatase (TRAP) staining clustered in the perinuclear area
• osteoclasts cultured on bone show barely detectable localization of LAMP-2 positive lysosomes at the ruffled border and CTSK (cathepsin K) secretion in the resorption lacuna, while the sealing zone appears intact, indicating defects in lysosome peripheral distribution and ruffled border formation
• osteoclasts cultured on glass have lysosomes clustered at the perinuclear region as opposed to the cell periphery
• in vitro osteoclast differentiation and the cytoskeletal organization of actin and microtubules are relatively normal in osteoclasts cultured on glass and bone
• in vivo, osteoclast number and surface are similar to those in control mice
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• in vitro, the bone resorption capacity of osteoclasts cultured on bone slices is markedly decreased, as shown by resorption pit staining and the amount of CTx-I (a bone resorption marker) released in the culture medium
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| autosomal recessive osteopetrosis 6 | DOID:0110945 |
OMIM:611497 |
J:236517 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• partial decrease in spread osteoclast like cells in vitro
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• activity of osteoclast like cells is reduced in vitro
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• clubbing of the long bones with decreased marrow space
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• cartilage remnants from the growth plate are found in the metaphysis a pathological feature of osteopetrosis
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• decreased marrow space
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• trabecular spacing is reduced
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• at 3 and 8 weeks of age
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• partial decrease in spread osteoclast like cells in vitro
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• activity of osteoclast like cells is reduced in vitro
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• partial decrease in spread osteoclast like cells in vitro
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• activity of osteoclast like cells is reduced in vitro
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Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO) |
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last database update 04/30/2024 MGI 6.23 |
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