Phenotypes Associated with This Genotype

Genotype
MGI:5907609

• Allelic Composition: Tg(MT2A-TGFBR2)4Rser/0
• Genetic Background: involves: C57BL/6 * DBA

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

skeleton

osteoarthritis ( J:44579 )

• progressive degeneration of cartilage resembling osteoarthritis in joints of older mice

• joints of older mice with mild degeneration exhibit fibrillated and disorganized articular cartilage and deeper chondrocytes are grouped into clusters

• joints with more severe degeneration show replacement of articular cartilage with hypertrophic cartilage and bone

• stiffness in the hindlimb joints

abnormal skeleton morphology ( J:44579 )

• skeletal defects are apparent by 3 months of age and become progressively worse with age

• however, E17.5 fetuses do not exhibit defects in size or shape of long bones or vertebrae

abnormal tibia morphology ( J:44579 )

• in the most severe cases, the femur is pressed into the tibia and the entire surface of the tibia is destroyed

abnormal sternum morphology ( J:44579 )

• sternal defects

abnormal xiphoid process morphology ( J:44579 )

• the xiphoid process of the sternum protrudes out from the chest

split xiphoid process ( J:44579 )

• xiphoid process is bifurcated in adults

split sternum ( J:44579 )

• fusion of the sternum is incomplete in 64% of E17.5 fetuses, with varied degree of sternal bifurcation

kyphoscoliosis ( J:44579 )

abnormal vertebrae morphology ( J:44579 )

• vertebrae are often misshapen

osteophytes ( J:44579 )

• early osteophytes are present as outgrowths of chondroid tissuein the articular margins

abnormal cartilage morphology ( J:44579 )

• mice exhibit less proteoglycan but more type X collagen localized in the cartilage matrix

abnormal joint morphology ( J:44579 )

• knee and shoulder joints are disorganized

• cartilaginous metaplasia is seen in synovium filling the joint space

vertebral fusion ( J:44579 )

• vertebrae often appear fused

abnormal articular cartilage morphology ( J:44579 )

• some degeneration of the articular surface in knee joints is seen at 4 weeks of age, with patches of articular surface denuded of cartilage and hypertrophic cells in the articular cartilage

abnormal synovial joint capsule morphology ( J:44579 )

• the synovium is hyperplastic and thrown into folds

• detached fragments of bone covered with cartilage is seen in the joint space

calcified joint ( J:44579 )

• knee and shoulder joints contain excess calcified tissue

abnormal epiphyseal plate morphology ( J:44579 )

• organization and histology of the growth plate is altered at 4 and 8 weeks of age

• a population of small, round cells is located between the proliferating and hypertrophic zones in 4 week old mice

• very few proliferating cells are seen in the growth plate at 8 weeks of age and most cells are hypertrophic and abnormally round

• disorganized zones of cartilage are often seen in the epiphyseal head of long bones at all ages

• growth plate is often disorganized or undetectable in bones from older mice

abnormal long bone epiphyseal plate proliferative zone ( J:44579 )

• cells in the proliferating zone are sometimes grouped into clusters in 4 week old mice

increased width of hypertrophic chondrocyte zone ( J:44579 )

• at 4 weeks of age, the hypertrophic zone is thicker and the cells in this zone are not organized in columnar arrays

homeostasis/metabolism

calcinosis ( J:44579 )

• tumoral calcinosis in 4 of 19 mice

immune system

osteoarthritis ( J:44579 )

• progressive degeneration of cartilage resembling osteoarthritis in joints of older mice

• joints of older mice with mild degeneration exhibit fibrillated and disorganized articular cartilage and deeper chondrocytes are grouped into clusters

• joints with more severe degeneration show replacement of articular cartilage with hypertrophic cartilage and bone

• stiffness in the hindlimb joints

limbs/digits/tail

abnormal hindlimb morphology ( J:44579 )

• hindlimbs are torqued laterally at varying angles in some cases

abnormal tibia morphology ( J:44579 )

• in the most severe cases, the femur is pressed into the tibia and the entire surface of the tibia is destroyed

neoplasm

increased tumor incidence ( J:44579 )

• tumoral calcinosis-like lesions, most often near the cervical vertebrae, although masses are seen along the vertebral column, in the axilla and pelivis, and in the paws

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
osteoarthritis		DOID:8398		J:44579