Analysis Tools
skeleton
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• about 30% of P1 mutants exhibit abnormal formation of tarsal bones
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• ribs are distorted due to abnormal ossification
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• decrease in bone density except in areas where osteophytes form
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• P40 mutants show decreased proteoglycan content in articular cartilage and growth plates
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• enhancement of terminal differentiation of epiphyseal growth plate chondrocytes shortly after weaning
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• knee joints are enlarged due to osteophytes that develop at the joint margins and within the joint space; osteophytes are also found in sternum and vertebral bone joints
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• synovial joint formation is normal, however mutants exhibit progressive articular cartilage degeneration
• the articular surface of joints with mild degeneration is covered with abnormally differentiated chondrocytes instead of a thin layer of resting chondrocytes
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• surface fibrillation (vertical cleft development) and osteophytes with varying sizes are seen in synovial cavities of most 6 month old mutants; osteophytes contain both chondrocytes and osteoblasts in the outgrowth of endochondral tissues
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• abnormal calcification of the synovial joints is seen in mutants over 6 months of age
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• growth plates of P21 or older mutants contain fewer proliferating chondrocytes than controls
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• gradual increase in the height of the hypertrophic zone is seen in some 3-4 week old mutants and becomes more pronounced at 6-8 weeks of age
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• bone rudiments from E17.5 metatarsals exhibit a diminished response to TGF-beta1 inhibition and do not show repression of hypertrophic zone expansion as is seen in controls
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• progressive loss of articular cartilage leading to the development of degenerative joint disease
• formation of large osteophytes in joints
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digestive/alimentary system
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• 7%-10% of mice die from intestinal abscesses by 3 months of age
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immune system
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• monocytes show a selectively blunted chemotatic response to TGF-beta
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• bone marrow-derived, IL-7- dependent pro-B lymphocytes fail to exhibit a TGFbeta induced increased in apoptosis following a 24 or 48 hour treatment
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• progressive loss of articular cartilage leading to the development of degenerative joint disease
• formation of large osteophytes in joints
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endocrine/exocrine glands
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• at P2, the number of primary follicles per ovary is significantly lower than that in wild-type ovaries
• however, the number of healthy primary follicles is not significantly different at P7 or P18
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• at P7, the number of primordial follicles per ovary is significantly higher than that in wild-type ovaries
• by P90, ovaries contain 2.7-fold more primordial follicles than wild-type ovaries
• at P18, ovaries contain ~61% more primordial follicles than wild-type ovaries
• however, no significant change in seen at P2, indicating a normal size of primordial follicle pool at birth
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• at P7, ovaries contain significantly fewer preantral follicles than wild-type ovaries
• at P18, ovaries contain 40% fewer preantral and antral follicles than wild-type ovaries
• by P90, ovaries contain 3-fold fewer preantral and antral follicles than wild-type ovaries
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• at P7, ovaries contain significantly fewer preantral and antral follicles than wild-type ovaries
• at P18, ovaries contain 40% fewer preantral and antral follicles than wild-type ovaries
• by P90, ovaries contain 3-fold fewer preantral and antral follicles than wild-type ovaries
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• ovarian follicular development is impaired during adult life, as ovaries isolated at P7-P90 contain higher numbers of primordial follicles and lower numbers of large preantral and antral follicles than wild-type ovaries
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growth/size/body
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• mice are significantly smaller than wild-type and heterozygous controls
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• at P2, P7, P18 and P90, body weight is significantly lower than that in wild-type controls
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homeostasis/metabolism
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• mutants show accelerated cutaneous wound healing compared with wild-type, characterized by an increased rate of re-epithelialization and reduced local infiltration of monocytes
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• mutants exhibit protection against tubulointerstitial fibrosis following unilateral ureteral obstruction as evidenced by blocking of the epithelial-mesenchymal transition and abrogation of monocyte influx and collagen accumulation
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mortality/aging
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• 7%-10% of mice die from intestinal abscesses by 3 months of age
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renal/urinary system
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• cultured primary renal tubular epithelial cells do not respond to TGF-beta1 and do not undergo the epithelial-to-mesenchymal transition (EMT) as wild-type cells and retain features of an epithelial monolayer
• cyclic mechanical stretching of mutant renal tubular epithelial cells in culture does not elicit EMT as in wild-type
• mutant epithelial cells show no phenotypic change when cocultured with monocytes unlike wild-type which show a fibroblastic appearance (exhibit EMT)
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behavior/neurological
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• mutants show progressive loss of movement due to degenerative joint disease
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reproductive system
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• at P2, the number of primary follicles per ovary is significantly lower than that in wild-type ovaries
• however, the number of healthy primary follicles is not significantly different at P7 or P18
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• at P7, the number of primordial follicles per ovary is significantly higher than that in wild-type ovaries
• by P90, ovaries contain 2.7-fold more primordial follicles than wild-type ovaries
• at P18, ovaries contain ~61% more primordial follicles than wild-type ovaries
• however, no significant change in seen at P2, indicating a normal size of primordial follicle pool at birth
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• at P7, ovaries contain significantly fewer preantral follicles than wild-type ovaries
• at P18, ovaries contain 40% fewer preantral and antral follicles than wild-type ovaries
• by P90, ovaries contain 3-fold fewer preantral and antral follicles than wild-type ovaries
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• at P7, ovaries contain significantly fewer preantral and antral follicles than wild-type ovaries
• at P18, ovaries contain 40% fewer preantral and antral follicles than wild-type ovaries
• by P90, ovaries contain 3-fold fewer preantral and antral follicles than wild-type ovaries
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• ovarian follicular development is impaired during adult life, as ovaries isolated at P7-P90 contain higher numbers of primordial follicles and lower numbers of large preantral and antral follicles than wild-type ovaries
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limbs/digits/tail
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• about 30% of P1 mutants exhibit abnormal formation of tarsal bones
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• although most of the bones in young mutants are normal, about 30% of P1 mice exhibit unilateral or bilateral angular distortion in their forelimbs due to abnormal formation of tarsal bones
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integument
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• primary keratinocytes in culture show reduced sensitivity to growth inhibition by TGF-beta and reduced adhesion to matrix and migration towards TGF-beta and keratinocyte growth factor
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cellular
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• bone marrow-derived, IL-7- dependent pro-B lymphocytes fail to exhibit a TGFbeta induced increased in apoptosis following a 24 or 48 hour treatment
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hematopoietic system
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• monocytes show a selectively blunted chemotatic response to TGF-beta
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• bone marrow-derived, IL-7- dependent pro-B lymphocytes fail to exhibit a TGFbeta induced increased in apoptosis following a 24 or 48 hour treatment
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| osteoarthritis | DOID:8398 | J:68792 | ||
