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Phenotypes Associated with This Genotype
Genotype
MGI:3760091
Allelic
Composition
Smad3tm1Cxd/Smad3tm1Cxd
Genetic
Background
involves: 129S6/SvEvTac
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Smad3tm1Cxd mutation (0 available); any Smad3 mutation (3 available)
phenotype observed in females
phenotype observed in males
N normal phenotype

Skeletal defects in 7 month old Smad3tm1Cxd/Smad3tm1Cxd mice

skeleton
• about 30% of P1 mutants exhibit abnormal formation of tarsal bones
• ribs are distorted due to abnormal ossification
• decrease in bone density except in areas where osteophytes form
• P40 mutants show decreased proteoglycan content in articular cartilage and growth plates
• enhancement of terminal differentiation of epiphyseal growth plate chondrocytes shortly after weaning
• 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
• 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
• 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
• abnormal calcification of the synovial joints is seen in mutants over 6 months of age
• growth plates of P21 or older mutants contain fewer proliferating chondrocytes than controls
• 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
• 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
• progressive loss of articular cartilage leading to the development of degenerative joint disease
• formation of large osteophytes in joints

immune system
• monocytes show a selectively blunted chemotatic response to TGF-beta
• 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
• progressive loss of articular cartilage leading to the development of degenerative joint disease
• formation of large osteophytes in joints

homeostasis/metabolism
• mutants show accelerated cutaneous wound healing compared with wild-type, characterized by an increased rate of re-epithelialization and reduced local infiltration of monocytes
• 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

renal/urinary system
• 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)

behavior/neurological
• mutants show progressive loss of movement due to degenerative joint disease

limbs/digits/tail
• about 30% of P1 mutants exhibit abnormal formation of tarsal bones
• 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

integument
• 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

cellular
• 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

hematopoietic system
• monocytes show a selectively blunted chemotatic response to TGF-beta
• 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

Mouse Models of Human Disease
DO ID OMIM ID(s) Ref(s)
osteoarthritis DOID:8398 OMIM:140600
OMIM:165720
OMIM:607850
OMIM:610839
OMIM:612400
OMIM:612401
J:68792


Contributing Projects:
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Tumor Biology (MTB), Gene Ontology (GO), MouseCyc
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last database update
02/05/2019
MGI 6.13
The Jackson Laboratory