Hepatitis C animal model

Details Hepatitis C animal model Hepatitis C animal model

2000-09-14

2002-08-06

Crouch, Deborah (Department: 1632)

Multicellular living organisms and unmodified parts thereof and

Nonhuman animal

Transgenic nonhuman animal

C800S003000, C800S009000, C800S025000

Reexamination Certificate

active

06429355

ABSTRACT:

This application is a 371 of PCT/JP97/02675 filed Jul. 24, 1997.
TECHNICAL FIELD OF THE INVENTION
The present invention relates to a hepatitis C animal model, which is useful for clarification of an onset mechanism of hepatitis C, development of means for treating the disease, and so on.
BACKGROUND OF THE INVENTION
Until now, many attempts have been made to produce an onset model of hepatitis by introducing a hepatitis C virus (hereinafter, referred to as “HCV”) gene into a small animal such as mouse and expressing the introduced gene (C. Pasquinelli et al., Abstract book of 2nd international meeting on hepatitis C virus and related viruses (Jul. 31-Aug. 5, 1994 San Diego, USA); C. Pasquinelli et al., Abstract book of 3rd international meeting on hepatitis C virus and related viruses (Aug. 28-Sep. 3, 1995 Gold coast, Australia); Kazuhiko Koike et al., J. General Virology 76 pp.3031-3038 1995; and T. Kato, Arch Virol 141 pp.951-958 1996). However, unlike many other genes, the HCV gene was difficult to be integrated into a murine individual, and even if it was successfully integrated into the animal, production of an HCV protein did not take place in most cases. Furthermore, even in the extremely rare case where an HCV protein was produced in the animal, use as a hepatitis model was impossible since the protein was produced from the fetal period, thereby causing an immunological tolerance which resulted in no animal exhibiting typical hepatitis symptoms after birth.
PROBLEM TO BE SOLVED BY THE INVENTION
In clarifying an onset mechanism of a human disease and developing means for treating the disease, an animal model presenting pathological conditions very similar to those of the disease plays an important role.
However, as described above, a hepatitis C animal model has not yet been produced, and this has been one of the obstacles in clarifying the onset mechanism of hepatitis C.
The present invention arises from such a technical background. An object of the present invention is to provide a novel animal model that exhibits the pathological conditions analogous to human hepatitis C.


REFERENCES:
patent: 6201166 (2001-03-01), Kohara et al.
Wall; Transgenic Livestock: Progress and Prospects for the Future, 1996, Theriogenology 45:57-68.*
Araki et. al.; Efficiency of Recombination by Cre Transient Expression in Embryonic Stem Cells: Comparison of Various Promoters, 1997, J. Biochem 122: 977-982.*
Yamamota, M., et al,In Vivo Transfection of Hepatitis C Virus Complementary DNA Into Rodent Liver by Asialoglycoprotein Receptor Mediated Gene Delivery, Hepatology, vol. 22 (3), pp. 847-855 (1995).
Takehara, T., et al.,Expression of the Full-Coding Sequence of the Hepatitis C Virus Genome in Adult Rat Liver Using Cationic Liposome-Mediated In Vivo Gene Transfer, Hepatology, vol. 20, p. 232A (1994).
Koike, K. et al.,Expression of Hepatitis C Virus Envelope Proteins in Transgenic Mice, J. Gen. Virol., vol. 76, pp. 3031-3038 (1995).
Kato, T., et al.,Inactivation of Hepatitis C Virus cDNA Transgene by Hypermethylation in Transgenic Mice, Arch. Virol., vol. 141, pp. 951-958 (1996).
Sternberg, N., et al.,Bacteriophage P1 Site-specific Recombination, J. Mol. Biol., vol. 150, pp. 487-507 (1981).

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