Chimeric mice that are produced by microcell mediated chromosome transfer and that retain a human antibody gene
AssigneeKirin Beer Kabushiki Kaisha
InventorsKazuma Tomizuka, Hitoshi Yoshida, Kazunori Hanaoka, Mitsuo Oshimura, Isao Ishida
Life of this patent
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Abstract
A chimeric, non-human animal can be produced by a method that entails providing a microcell that contains one or more foreign chromosomes or fragment(s) thereof and then fusing the microcell with a pluripotent cell, thereby introducing the foreign chromosome(s) or fragment(s) into the latter. The pluripotent cell thus obtained can be used to generate a chimeric, non-human animal, the cells, tissues, and/or progeny of which can be the source of a product, such as an antibody, that is associated with one or more genes on the foreign chromosome(s) or fragment(s).
Claims54
A method for producing a chimeric mouse wherein at least some mouse cells retain a foreign chromosome(s) or a fragment(s) thereof, which method comprises:
- 1) preparing a microcell retaining a foreign chromosome(s) or a fragments thereof that comprise a human antibody gene;
- 2) transferring the foreign chromosome(s) or fragment(s) thereof into a pluripotent mouse cell by fusion with the microcell;
- 3) transferring the pluripotent mouse cell into a mouse embryo;
- 4) transferring the mouse embryo into a uterus or oviduct of a pseudo-pregnant female mouse;
- and
- 5) allowing said mouse embryo to develop into said chimeric mouse.
A method for producing a pluripotent mouse cell retaining a foreign chromosome(s) or a fragment(s) thereof, which comprises preparing a microcell retaining a foreign chromosome(s) or a fragment(s) thereof and transferring the foreign chromosome(s) or fragment(s) thereof into a pluripotent mouse cell by fusion with the microcell, wherein the foreign chromosome(s) or fragment(s) thereof comprise a human antibody gene.
A pluripotent mouse cell which retains a human-derived chromosome(s) or a fragment(s) thereof having a base length not less than 1 Mb, and which can express the gene(s) on the human-derived chromosome(s) or fragment(s) thereof after the differentiation of the cell, wherein the human-derived chromosome(s) or fragment(s) thereof comprise a human antibody gene.
A mouse wherein at least some mouse cells retain a foreign chromosome(s) or a fragment(s) thereof, wherein said foreign chromosome(s) or a fragment(s) thereof is independently maintained from the mouse chromosomes and/or has a base length not less than 1 Mb, and wherein the foreign chromosome(s) or fragment(s) thereof comprise a human antibody gene.
A mouse wherein at least some mouse cells retain a human-derived chromosome(s) or a fragment(s) thereof having a base length not less than 1 Mb, and which can express the gene(s) on the human-derived chromosome(s) or fragment(s) thereof, wherein at least one of the genes expressed on the human-derived chromosome(s) or fragment(s) is a human antibody gene.
A mouse wherein at least some mouse cells retain a human-derived DNA fragment(s) comprising human antibody gene, having a base length not less than 1 Mb and/or independently maintained from the mouse chromosome, wherein the mouse is capable of expressing the human antibody gene.
A mouse wherein at least some mouse cells retain a human-derived chromosome(s) or a fragment(s) thereof containing a human antibody gene and having a base length not less than 1 Mb, and which can express at least one class or subclass of the human antibody.
A mouse wherein at least some mouse cells retain a human antibody gene having a base length not less than 1 Mb, and which can express at least one class or subclass of the human antibody.
Dependencies are inferred from the claim text.