IN VIVO GENE REGULATION BY THE COMBINATION OF KNOCK- IN-TETO SEQUENCE INTO THE GENOME AND TETRACYCLINE-CONTROLLED TRANS-SUPPRESSOR (TTS) PROTEIN

摘要

Disclosed is a FAST (Flexible Accelerated STOP TetO-knocfan) system, an efficient method for manipulating gene expression in vivo to rapidly screen animal models of disease This invention further discloses a single gene targeting event yielding 2 distinct knoctan mice -STOP tetO and tetO knockm- which permit generation of multiple strains with variable expression patterns 1) knockout, 2) Cre mediated rescue, 3) tTA mediated misexpression, 4) tTA-mediated overexpression, and 5) tTS mediated conditional knockout/knockdown Using the FAST system, multiple gam- and loss of function strains can therefore be generated on a timescale not previously achievable These strains can then be screened for clinically relevant abnormalities The flexibility and broad applicability of the FAST system is demonstrated by targeting several genes encoding proteins implicated in neuropsychiatry disorders MIc 1, Neurohgin 3, the serotonin IA receptor, and the serotonin IB receptor.