Nonhuman animal and use for same
AssigneesInter-University Reseach Institute Corporation Research Organization of Informaton and Systems, Kake Educational Institution
InventorsMasato Kanemaki, Ken-Ichiro Hayashi, Naomi Kitamoto, Yumiko Saga, Rieko Ajima
Life of this patent
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Abstract
A genetically modified non-human animal in which an auxin-inducible degron system controls degradation of a target protein in a living body includes: a chromosome containing a first nucleic acid that encodes a mutant TIR1 family protein having a mutation at an auxin-binding site and having affinity to an auxin analog.
Claims4
A method for evaluating a drug discovery target protein or a drug, comprising:
- administering an auxin analog intraperitoneally or orally in an effective amount of 10 mg/kg or less per day to a genetically modified rodent wherein the genetically modified rodent has an auxin-inducible degron system that controls degradation of a target protein in a living body comprising:
- a chromosome containing a first nucleic acid that encodes a mutant TIR1 family protein having a mutation at an auxin-binding site and having an affinity to an auxin analog,
- a chromosome including a second nucleic acid that encodes a degradation tag containing at least a part of an Aux/IAA family protein and having an affinity to the complex of the mutant TIR1.
A method for evaluating a drug discovery target protein, comprising:
- Step 1 of administering an auxin analog intraperitoneally or orally in an effective amount of 10 mg/kg or less per day to a genetically modified rodent which has a tissue-specific disease, in which an auxin-inducible degron system controls degradation of a target protein in a living body, and which has cells, throughout the body, containing a chromosome containing a first nucleic acid that encodes a mutant TIR1 family protein having a mutation at an auxin-binding site and having an affinity to the auxin analog, and
- a chromosome containing a second nucleic acid that encodes a degradation tag containing at least a part of an Aux/IAA family protein and having an affinity to a complex of the mutant TIR1 family protein and the auxin analog and a third nucleic acid that encodes a target protein linked upstream or downstream of the second nucleic acid are provided to cells throughout the body thereof, wherein the mutant TIR1 family protein is a protein in which an F74 of OsTIR1 has mutated to A, G, or S,
- wherein the auxin analog is a compound represented by the following general formula (I) or an ester thereof:
- and wherein R10 is a cyclic aliphatic hydrocarbon group in which a substituent may be present and some carbon atoms that configure a ring may be substituted with heteroatoms or an aromatic hydrocarbon group in which a substituent may be present and some carbon atoms that configure a ring may be substituted with heteroatoms;
- Step 2 of inducing, by the auxin-inducible degron system, degradation of the target protein in the living body in each cell;
- and
- Step 3 of observing an influence of the degradation of the target protein on diseased tissues and normal tissues.
Dependencies are inferred from the claim text.