AC5 knock-out mouse with hypoalgesia and screening method of compound for inhibiting pain

摘要

Provided are an AC5(type 5 adenylyl cyclase) knock-out mouse with hypoalgesia which shows a phenotype of hypoalgesia by deletion of AC5 gene in a mouse and a screening method of compound for inhibiting pain, so that a mechanism related to pain is identified and the compound for inhibiting pain is screened. The AC5 knock-out mouse with hypoalgesia is produced by (a) obtaining an AC5 genomic DNA clone containing an AC5 gene, (b) preparing an AC5 knock-out cassette from the AC5 genomic DNA clone, (c) transfecting an embryonic stem cell with the AC5 knock-out cassette, (d) introducing the transfected embryonic stem cell into a blastocoele of a blastocyst, (e) transplanting the blastocoele containing the embryonic stem cell into the womb of a surrogate mother to obtain a chimera mouse, (f) hybridizing the F1 transformed mouse to obtain a heterozygote F1 transformed mouse having genotype of AC5^+/-, and (g) hybridizing the heterozygote F1 transformed mouse to obtain a homozygote F2 transformed mouse having genotype of AC5^-/-. The method for screening the compound for inhibiting pain comprises the steps of: (a) measuring the reaction degree against pain stimulation of the AC5^-/- transformed mouse and an AC5+/+ wild mouse; (b) administering testing compounds into the AC5^-/- transformed mouse and AC5+/+ wild mouse and measuring the reaction degree against pain stimulation; and (c) comparing the reaction degrees against pain stimulation before and after the administration, and selecting a compound capable of increasing the reaction decrease rate of AC5^-/- transformed mouse compared to that of AC5+/+ wild mouse.