Temporal and spatially controlled APP transgene expression using Cre-dependent alleles

Although a large number of mouse models have been made to study Alzheimer???s disease, only a handful allow experimental control over the location or timing of the protein being used to drive pathology. Other fields have used the Cre and the tamoxifen-inducible CreER driver lines to achieve precise spatial and temporal control over gene deletion and transgene expression, yet these tools have not been widely used in studies of neurodegeneration. Here, we describe two strategies for harnessing the wide range of Cre and CreER driver lines to control expression of disease-associated amyloid precursor protein (APP) in modeling Alzheimer???s amyloid pathology. We show that CreER-based spatial and temporal control over APP expression can be achieved with existing lines by combining a Cre driver with a tetracycline-transactivator (tTA)-dependent APP responder using a Cre-to-tTA converter line. We then describe a new mouse line that places APP expression under direct control of Cre recombinase using an intervening lox-stop-lox cassette. Mating this allele with a CreER driver allows both spatial and temporal control over APP expression, and with it, amyloid onset.

Automated summary

This paper describes two strategies for controlling disease-associated amyloid precursor protein (APP) expression in modeling Alzheimer's amyloid pathology using Cre and CreER mouse lines. The first strategy combines a Cre driver with a tetracycline-transactivator (tTA)-dependent APP responder to achieve spatial and temporal control over APP expression. The second strategy involves using an intervening lox-stop-lox cassette to directly control APP expression through Cre recombinase, which can be paired with a CreER driver for spatial and temporal control.