[Analysis of HAM rat disease developed in HTLV-I carrier rat as an animal model of HAM/TSP in human].
Human T cell leukemia virus type I (HTLV-I) can be transmitted into several inbred strains of rats. Adult rats inoculated with HTLV-I immortalized human T cell line MT-2 at 8-37 weeks of age become seropositive HTLV-I carrier rats. Seropositive HTLV-I carrier rats of WKAH strain developed myelopathy similar to HAM/TSP (HTLV-I associated myelopathy/Tropical spastic paraparesis), designated as HAM rat disease. Neuropathological and immunohistochemical features of the affected spinal cord showed symmetrical white matter degeneration characterized by loss of myelin, vacuolar degeneration, infiltration with foamy macrophages and astrocytic gliosis. Lymphocytic infiltration was virtually absent throughout the disease process, and apoptotic cells were observed in the affected spinal cord. Clinical findings and pathological changes in seropositive HAM rats were, in general, milder than findings in seronegative HAM rats as previously described. Provirus genome in the affected spinal cord was evident in 1 of 2 seropositive HAM rats by polymerase chain reaction, but localization of HTLV-I antigen could not be detected by immunohistochemical staining. The collective evidence suggests that development of HAM rat disease is under strict genetic restriction of the host strain, and the primary cause is not mediated by immunological process with effector T cells as suggested in human HAM/TSP, and there seems to be a direct or indirect neurotoxicity for oligodendrocytes mediated by HTLV-I infection.
Third Department of Internal Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
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D000818:Animals; D017209:Apoptosis; D002353:Carrier State; D004195:Disease Models, Animal; D015490:HTLV-I Infections / Q000473:pathology; D006801:Humans; D008264:Macrophages / Q000473:pathology; D015493:Paraparesis, Tropical Spastic / Q000235:genetics / Q000473:pathology; D051381:Rats; D011919:Rats, Inbred Strains; D013116:Spinal Cord / Q000473:pathology