Patent ID: 9084814
Filing Date: 2015-07-21
Classification: A01K,A61K,C12N,G01N

Abstract:
1. A method for screening for agents that inhibit Mst activity comprising: (a) administering a test agent to a transgenic non-human mammal that has been administered a control factor selected from tetracycline and doxycycline and thereby conditionally overexpresses myostatin (Mst), said transgenic non-human mammal having a genome that comprises a conditional bicistronic myostatin expression nucleic acid construct selected from the group of nucleic acid constructs consisting of: i) a) polyA-green fluorescence protein (EGFP)/internal ribosome entry site (IRES)-Mst/hemagglutinin (HA)-tetracycline response element (TRE)//MCK-rtTA/blue fluorescence protein (BFP)-polyA, b) polyA-BFP/rtTA-MCK//TRE-HA/Mst-IRES/EGFP-polyA, c) TRE-HA/Mst-IRES/EGFP-polyA//MCK-rtTA/BFP-polyA, d MCK-rtTA/BFP-polyA//TRE-HA/Mst-IRES/EGFP-polyA, e) TRE-HA/Mst-IRES/EGFP-polyA//polyA-BFP/rtTA-MCK, or f) MCK-rtTA/BFP-polyA//polyA-EGFP/IRES-Mst/HA-TRE; ii) any one of the constructs of a) lacking a HA tag; iii) any one of the constructs of a) lacking an IRES/EGFP or EGFP/IRES; and iv) any one of the constructs of a) lacking a BFP fusion to the rtTA sequence; wherein MCK is a promoter selected from muscle specific creatine kinase, MCK-3E, and troponin I; and wherein, in the absence of said test agent, said administration of said control factor results in Mst overexpression and decreased muscle mass as compared to control wild-type mammals; (b) measuring skeletal muscle mass in said transgenic non-human mammal administered said test agent; and (c) identifying the test agent as an agent that inhibits Mst activity based on the effects of the test agent on decreased skeletal muscle mass of the transgenic non-human mammal overexpressing Mst.