Osteochondrodysplasia occurring in transgenic mice expressing interferon-gamma.
In addition to various biological activities, interferon-gamma (IFN-gamma) inhibits bone resorption and collagen synthesis. We produced a transgenic mouse line expressing the murine IFN-gamma gene and protein in the bone marrow and thymus. Forty-five transgenic FVB/NCr mice, 23 days-9 months of age, were studied for anomalies in the skeletal system. The transgenic mice had short, wide, and deformed long bones. Young transgenic mice had epiphyseal plates severely thickened with zones of hypertrophy and degeneration with irregular metaphyseal borders. Cartilagenous masses were also observed in the metadiaphyseal marrow cavities. These lesions were primarily seen in long bones and ribs. Adult transgenic mice had residues of degenerated cartilagenous masses in the diaphyses. Many osteoclasts with well-developed ruffled borders were present on the metaphyseal cartilagenous masses in young transgenic mice. Adult transgenic mice had less prominent primary spongiosa with fewer osteoclasts at the metaphysis as compared with nontransgenic controls. The cortical bones of the transgenic mice were thinner and more immature compared with controls. Transgenic mice also had fractures, disruption of the epiphyseal plate, and degeneration of articular cartilage. Thus, the IFN-gamma transgenic mice developed a complex chondro-osseous lesion that was diagnosed as osteochondrodysplasia. The lesions may originate from primarily decreased matrix synthesis in bone and cartilage and also possible osteoclast-related changes caused by IFN-gamma overexpression in the bone marrow. Our IFN-gamma transgenic mouse will be a useful model to investigate the role of IFN-gamma in bone metabolism.
Nii
A
A
Veterinary and Tumor Pathology Section, National Cancer Institute, Frederick, MD, USA. nii_a@yamanouchi.co.jp
Reynolds
D A
DA
Young
H A
HA
Ward
J M
JM
D000135:Acid Phosphatase / Q000032:analysis; D000818:Animals; D000943:Antigens, Differentiation / Q000032:analysis; D001853:Bone Marrow / Q000737:chemistry / Q000378:metabolism; D001842:Bone and Bones / Q000737:chemistry / Q000000981:diagnostic imaging / Q000473:pathology; D003094:Collagen / Q000032:analysis / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D037502:Galectin 3; D005786:Gene Expression Regulation; D006132:Growth Plate / Q000737:chemistry / Q000000981:diagnostic imaging / Q000473:pathology; D007150:Immunohistochemistry / Q000379:methods; D015994:Incidence; D007371:Interferon-gamma / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D007527:Isoenzymes / Q000032:analysis; D008297:Male; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics* / Q000378:metabolism*; D008854:Microscopy, Electron / Q000379:methods / Q000662:veterinary; D010009:Osteochondrodysplasias / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D010010:Osteoclasts / Q000737:chemistry / Q000473:pathology / Q000648:ultrastructure; D011859:Radiography; D000071681:Tartrate-Resistant Acid Phosphatase; D013950:Thymus Gland / Q000737:chemistry / Q000378:metabolism
D000943:Antigens, Differentiation; D037502:Galectin 3; D007527:Isoenzymes; D007371:Interferon-gamma; D003094:Collagen; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase