PROBLEM TO BE SOLVED: To provide a model non-human animal that is useful for development of agent such as a chronic kidney disease therapeutic agent and is more superior than before as a model of a chronic kidney disease.SOLUTION: A life-shortened model non-human mammal is provided which is characterized by the function of the Agtrap gene being inhibited. In the non-human animal suffering a loss of ATRAP, the exacerbation of renal fibrosis (namely, chronic kidney disease, a state of a disease of terminal renal insufficiency) is observed, and the life is significantly shortened while abnormal conditions of other appearance are not present. Various retrogradation model mice conventionally known exhibit a wide variety of retrogradation traits in a whole body and have a clearly abnormal appearance. In the ATRAP deficit mouse, the abnormal conditions of the appearance are not present unlike these well-known retrogradation model mice, and the retrogradation trait itself is equal to wild type mice of the comparison. A model of the present invention is expected to greatly contribute even to the development of a therapeutic agent of the severe renal disease (chronic kidney disease containing terminal renal insufficiency) being irreversible and highly important.SELECTED DRAWING: Figure 2COPYRIGHT: (C)2017,JPO&INPIT【課題】慢性腎臓病治療薬等の開発に有用な、慢性腎臓病のモデルとして従来よりも優れたモデル非ヒト動物を提供すること。【解決手段】Agtrap遺伝子の機能が阻害されていることを特徴とする、寿命短縮化モデル非ヒト哺乳動物を提供した。ATRAPを欠損させた非ヒト動物では腎線維化の増悪(すなわち慢性腎臓病、末期腎不全の病態)が見られ、その他外観の異常がないまま寿命が有意に短縮化する。従来知られている各種の老化モデルマウスは、全身に広範な老化形質を呈し、明らかに異常な外観を有するが、ATRAP欠損マウスではこれらの公知の老化モデルマウスとは異なり、外観の異常がなく、老化形質自体は対照の野生型マウスと同等である。本発明のモデルは不可逆的とされ重要度が高い重症腎疾患(末期腎不全を包含する慢性腎臓病)の治療薬の開発にも大いに貢献すると期待される。【選択図】図2
