Animal model for prostatic stromal hyperplasia

Abstract

The present invention provides an animal model for prostatic stromal hyperplasia, and a method for screening for a substance effective for preventing/treating human benign prostatic hyperplasia using the animal model. The animal model for prostatic stromal hyperplasia is produced by implanting the fetal urogenital sinus of a non-human animal under the skin or beneath the prostatic capsule of a non-human animal belonging to the species of the same as or different from the said animal. A substance effective for preventing/treating human benign prostatic hyperplasia can be screened by administering a test substance to the animal model and measuring the preventive or therapeutic effect of the test substance upon the implanted tissue (fetal urogenital sinus or tissue derived therefrom).

1 . A non-human animal model for prostatic stromal hyperplasia having an extraneous fetal urogenital sinus or tissue derived therefrom under the skin. 
     
     
         2 . A non-human animal model for prostatic stromal hyperplasia according to  claim 1 , wherein subcutaneous refers to abdominal subcutaneous. 
     
     
         3 . A non-human animal model of prostatic stromal hyperplasia according to  claim 1 , wherein the fetal urogenital sinus is donated from an animal belonging to the species of the same as or different from the non-human animal model for prostatic stromal hyperplasia. 
     
     
         4 . A non-human animal model for prostatic stromal hyperplasia according to  claim 1 , produced by subcutaneously implanting the fetal urogenital sinus of a non-human animal into a non-human animal belonging to the species of the same as or different from the said animal. 
     
     
         5 . A non-human animal model for prostatic stromal hyperplasia according to  claim 1 , wherein the animal donating the fetal urogenital sinus is a rat or mouse, and the non-human animal model for prostatic stromal hyperplasia is, the same or different, a non-human animal selected from a mouse, a nude mouse, a rat, and a nude rat. 
     
     
         6 . A method for producing a non-human animal model for prostatic stromal hyperplasia comprising the steps of:
 (i) subcutaneously implanting a fetal urogenital sinus of a non-human animal into a non-human animal belonging to the species of the same as or different from the said animal, and   (ii) forming stroma-enlarged tissue under the skin by rearing the urogenital sinus-implanted non-human animal, as required.   
     
     
         7 . A method for producing a non-human animal model for prostatic stromal hyperplasia according to  claim 6 , wherein a subcutaneous site where the fetal urogenital sinus is implanted is an abdominal subcutaneous site. 
     
     
         8 . A method for producing a non-human animal model for prostatic stromal hyperplasia according to  claim 6 , wherein step (i) comprises implanting the fetal urogenital sinus of a rat under the abdominal skin of a nude mouse. 
     
     
         9 . A method for screening for a substance effective for preventing or treating human benign prostatic hyperplasia comprising:
 administering a test substance to the non-human animal model for prostatic stromal hyperplasia of  claim 1 , and   measuring the preventive or therapeutic effect of the test substance on the extraneous fetal urogenital sinus or tissue derived therefrom of the non-human animal model for prostatic stromal hyperplasia.   
     
     
         10 . A method for screening for a substance effective for treating human benign prostatic hyperplasia comprising steps (a) to (c) below:
 (a) administering a test substance to the non-human animal model for prostatic stromal hyperplasia of claim ( 1 ), and rearing it;   (b) measuring the stromal area ratio or weight of extraneous urogenital sinus-derived tissue of the non-human animal model for prostatic stromal hyperplasia; and   (c) selecting a test substance that reduces the stromal area ratio or weight based on the result obtained in (b) in comparison with the stromal area ratio or weight of extraneous urogenital sinus-derived tissue of the non-human animal model for prostatic stromal hyperplasia before administering the test substance.   
     
     
         11 . A method for screening for a substance effective for preventing human benign prostatic hyperplasia comprising steps (a) to (c) below:
 (a) administering a test substance to the non-human animal model for prostatic stromal hyperplasia of claim ( 1 ), and rearing it;   (b) measuring the stromal area ratio or weight of extraneous urogenital sinus-derived tissue of the non-human animal model for prostatic stromal hyperplasia; and   (c) selecting a test substance that inhibits the increase of the stromal area ratio or weight based on the result obtained in (b) in comparison with the stromal area ratio or weight of extraneous urogenital sinus-derived tissue of a control non-human animal model for prostatic stromal hyperplasia that is not administered with the test substance.   
     
     
         12 . A pharmaceutical composition for preventing or treating human benign prostatic hyperplasia comprising as an active ingredient a substance selected according to the screening method of  claim 9 . 
     
     
         13 . A method for evaluating the preventive or therapeutic effect of a test substance on human benign prostatic hyperplasia comprising:
 administering a test substance to the non-human animal model for prostatic stromal hyperplasia of  claim 1 , and   measuring the preventive or therapeutic effect of administering the test substance on an extraneous fetal urogenital sinus or tissue derived therefrom.   
     
     
         14 . A method for evaluating the preventive or therapeutic effect of a test substance on human benign prostatic hyperplasia comprising:
 administering a test substance to the animal model for prostatic stromal hyperplasia of  claim 1 , and   measuring the change in stromal area ratio or weight of extraneous fetal urogenital sinus or tissue derived therefrom.   
     
     
         15 . A method for evaluating the therapeutic effect of a test substance on human benign prostatic hyperplasia comprising steps (a) and (b) below:
 (a) administering a test substance to the non-human animal model for prostatic stromal hyperplasia of  claim 1 , and rearing it; and   (b) comparing the stromal area ratio or weight of extraneous urogenital sinus-derived tissue of the non-human animal model for prostatic stromal hyperplasia with the stromal area ratio or weight of extraneous urogenital sinus-derived tissue of the non-human animal model of prostatic stromal hyperplasia before administering the test substance.   
     
     
         16 . A method for evaluating the preventive effect of a test substance against human benign prostatic hyperplasia comprising steps (a) and (b) below:
 (a) administering a test substance to the non-human animal model for prostatic stromal hyperplasia of  claim 1 , and rearing it; and   (b) comparing the stromal area ratio or weight of extraneous urogenital sinus-derived tissue of the non-human animal model for prostatic stromal hyperplasia with the stromal area ratio or weight of extraneous urogenital sinus-derived tissue of a corresponding control animal model for prostatic stromal hyperplasia that is not administered with the test substance.