Models of HTLV-I-induced diseases. Infectious transmission of HTLV-I in inbred rats and HTVL-I env-pX transgenic rats.
To examine the pathogenic roles of HTLV-I in HTLV-I-induced diseases, we developed two models; namely HTLV-I carrier rats and HTLV-I env-pX transgenic rats. Among life long HTLV-I carriers in seven rat strains, only WKAH rats with the RT1k haplotype developed chronic progressive myeloneuropathy, resembling HAM/TSP clinically and histologically in humans, designated as HAM rat disease and after long incubation periods. Apoptosis of myelin forming cells, oligodendrocytes and Schwann cells associated with HTLV-I infection appears to be the primary cause of HAM rat disease. Local activation of the pX gene and TNF alpha gene was evident in these rats. WKAH rats transgenic for HTLV-I env-pX gene were established and at age 5 weeks, swelling of the bilateral ankle joints began to develop and histological features of the affected joints resembled findings in cases of rheumatoid arthritis (RA): high-titers of rheumatoid factors were present in these rats. A series of vascular collagen diseases such as polyarteritis nodosa-like angiitis, polymyositis, myocarditis, and Sjögren's syndrome-like sialodenitis together with RA were present, even in one individual animal. These transgenic rats as well as HAM rats appear to be suitable animal models for elucidating pathogenic mechanisms implicated in HTLV-I-induced diseases and also various demyelinating vascular collagen diseases of unknown etiology.
Yoshiki
T
T
Department of Pathology, Hokkaido Univ. Sch. Med., Sapporo, Japan.
Ikeda
H
H
Tomaru
U
U
Ohya
O
O
Kasai
T
T
Yamashita
I
I
Morita
K
K
Yamazaki
H
H
Ishizu
A
A
Nakamaru
Y
Y
Kikuchi
K
K
Tanaka
S
S
Wakisaka
A
A
D000818:Animals; D030801:Animals, Genetically Modified; D001172:Arthritis, Rheumatoid / Q000503:physiopathology; D002353:Carrier State; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D015686:Gene Products, env / Q000096:biosynthesis / Q000235:genetics; D015752:Genes, env; D015490:HTLV-I Infections / Q000503:physiopathology / Q000635:transmission*; D015368:Human T-lymphotropic virus 1 / Q000235:genetics*; D015493:Paraparesis, Tropical Spastic / Q000503:physiopathology / Q000635:transmission*; D051381:Rats; D011919:Rats, Inbred Strains; D015682:Retroviridae Proteins, Oncogenic / Q000096:biosynthesis / Q000235:genetics*; D012217:Rheumatoid Factor / Q000032:analysis; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D054334:Viral Regulatory and Accessory Proteins
D015686:Gene Products, env; D015682:Retroviridae Proteins, Oncogenic; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D054334:Viral Regulatory and Accessory Proteins; C072343:pX protein, Human T-lymphotropic virus 1; D012217:Rheumatoid Factor