1996 Fiscal Year Final Research Report Summary
APOPTOSIS IN ANIMALS WITH IMMUNOLOGICAL DISORDERS
| Project/Area Number |
07456142
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Applied veterinary science
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| Research Institution | The University of Tokyo |
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Principal Investigator |
HASEGAWAA Atsuhiko The University of Tokyo, Grad.Sch.of Agri.and Life Sci., PROFESSOR, 大学院・農学生命科学研究科, 教授 (90011923)
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| Co-Investigator(Kenkyū-buntansha) |
WATARI Toshihiro The University of Tokyo, Grad.Sch.of Agri.and Life Sci., ASSISTANT PROFESSOR, 大学院・農学生命科学研究科, 助手 (50220950)
NAKAYAMA Hiroyuki The University of Tokyo, Grad.Sch.of Agri.and Life Sci., ASSOCIATE PROFESSOR, 大学院・農学生命科学研究科, 助教授 (40155891)
TSUJIMOTO Hajime The University of Tokyo, Grad.Sch.of Agri.and Life Sci., ASSOCIATE PROFESSOR, 大学院・農学生命科学研究科, 助教授 (60163804)
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| Project Period (FY) |
1995 – 1996
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| Keywords | APOPTOSIS / FAS ANTIGEN / FAS LIGAND / FELINE IMMUNO-DEFICINENCY VIRUS / LYMPHO10 TUMOR / P53 |
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| Research Abstract |
Fas antigen and Fas ligand, which are key molecules for induction of apoptosis, were molecularly cloned and exmined for their expression in feline lymphoid cells. Feline Fas antigen cDNA had a characteristic structure of typeI TNF receptor family consisting of 3 extracellular subdomains, a transmembrane domain and an intracellular death domain essential for induction of apoptosis. Feline Fas ligand cDNA clone had a structure of type II membrane protein of the TNF family containing prorine-rich stretch in the N-terminal intracellular region. Expression of Fas antigen was enhanced in feline lymphoid cells showing apoptosis after infection with feline immunodeficiency virus (FIV), however, expression of Fas ligand did not change after the virus infection.
On the other hand, induction of apoptosis in the peripheral blood from cats infected with FIV was examined by flowcytometiric analysis. Apoptosis wass found to be induced in a high proportion of feline lymphocytes derived from FIVinfected cats after cultivation for 24 hours. The induction of apoptosis was detected in all of the CD4 (+), PanT (+) and s-Ig (+) cell populations.
Inactivation of p53 gene which is a key molecule for apoptosis through induction of Bax was examined by PCR-SSCP and nucleotide sequencing analyzes. More than 70% of canine malignant tumors including osteosarcoma, colon cancer, acute myeloid leukemia and lymphoma had point mutation, deletion or insertion associated with inactivation of the basic function of p53 gene, indicating an important role of the inactivation of p53 gene in a variety of canine malignant tumors.
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