Characterization of a neural-specific inducible genetic system in transgenic mice

grantor: University of TorontoThis paper describes an attempt to utilize a recently developed system based upon prokaryotic control elements, the tetracycline transactivator system, to direct inducible expression of reporter gene sequences specifically in the nervous system of transgenic mice. The transactivator protein, tTA was placed under the control of the human neurofilament light chain gene promoter (pNFL) to give neural-specific expression. Although tTA mRNA expression was detectable by reverse transcriptase-polymerase chain reaction in the brains of pNFL-tTA transgenic mice, no reporter gene expression was observed when these mice were crossed to tet-O-$\beta$galactosidase transgenics. The most likely explanation for the lack of function is that the pNFL-tTA transgene sequences integrated into regions of the genome where proper transgene expression was prevented. Recent experiments from other laboratories have also suggested that an optimal level of tTA expression must be attained for proper functioning of the system. This is most conveniently done by choosing an appropriate promoter to drive tTA. It is possible that the human NFL promoter does not give this optimal level of tTA expression. Our laboratory is currently utilizing other neural-specific promoters to enable function of the tetracycline inducible system in neural tissue of transgenic mice. (Abstract shortened by UMI.)M.Sc