A technique that allows Escherichia coli, yeast, or the like to produce a useful protein by utilizing genetic recombination technologies, and a technique that administers such a protein to a mouse or the like as an antigen, and allows the mouse or the like to produce an antibody, are widely used at present.
However, a protein produced by a prokaryote such as Escherichia coli has not been accurately subjected to multimer formation and posttranslational modification such as glycosylation. A protein produced by yeast has not been subjected to complete posttranslational modification, and may not have the original functions.
In order to solve the above problem, a technique that allows insect cells or mammalian cells (e.g., mouse, pig, or human) to produce a useful protein has been used. However, this technique has problems in that a considerable cost is required to culture the cells, and it takes time to obtain a useful protein.
In view of the above situation, use of fish as a bioreactor has recently attracted attention. This technique has an advantage in that a protein derived from fish is subjected to multimer formation and posttranslational modification such as glycosylation in the same manner as a protein derived from a mammal. Patent Document 1 discloses a technique that allows a transgenic fish to produce a glycoprotein multimer by utilizing the above advantage, and collects the glycoprotein multimer from the embryo, larva, fry, tissue, or blood.
Fish can be raised relatively easily and inexpensively. It is very easy to care for fish since egg laying/collection can be controlled by controlling the water temperature, feeding, the duration of sunshine, the water quality, and the like.
The inventors of the invention developed various techniques such as a technique that produces an antigen-producing yeast, and administers the yeast to a fish (e.g., zebrafish) as feed to allow the fish to produce a specific antibody derived from the fish, and a technique that allows a fish to produce an antibody to a membrane protein such as a G protein-coupled receptor (GPCR) (that has been considered to be difficult) (Japanese Patent Application No. 2009-83900) (see Patent Documents 2 and 3, for example).
However, since these techniques collect the antibody from the whole body of the fish, it is impossible to repeatedly obtain the antibody produced by the fish while keeping the fish alive.
In order to solve the above problem, the inventors focused on fish bearing water vesicles (e.g., Bubble Eye) in the course of the development of the invention. Such goldfish are widely grown in Japan and overseas for ornamental purpose.
Patent Document 4 discloses that the blister fluid of a Bubble Eye has a function of protecting fish cells or promoting cell proliferation, and makes it possible to efficiently process fish cells in a state in which the quality of unfertilized eggs is maintained, for example.
However, Patent Document 4 does not even suggest allowing the blister fluid to produce a useful protein (e.g., antibody), and no attempts have been made to utilize a fish bearing water vesicles for production of an antibody.