Abstract
The spatial pattern of transgene expression in tetracycline-controlled mouse models is governed primarily by the driver line used to introduce the tetracycline-controlled transactivator (tTA). Detailed maps showing where each tTA driver activates expression are therefore essential for designing and using tet-regulated models, particularly in brain research where cell type and regional specificity determine the circuits affected by conditional gene expression. We have compiled a comprehensive online repository of serial microscopic images showing brain-wide reporter expression for five commonly used tTA driver lines. We have spatially registered all images to a common three-dimensional mouse brain anatomical reference atlas for direct comparison of spatial distribution across lines. The high-resolution images and associated metadata are shared via the web page of the EU Human Brain Project. Images can be inspected using an interactive viewing tool that includes an optional overlay feature providing anatomical delineations and reference atlas coordinates. Interactive viewing is supplemented by semi-quantitative analyses of expression levels within anatomical subregions for each tTA driver line.
Highlights
Background & SummaryTransgenic mice in which the expression of specific genes can be pharmacologically regulated are powerful tools for studying brain disease[1,2,3,4,5,6,7,8,9,10]
A database of tet-transgenic rodents lists more than a hundred mouse lines expressing tTA or its tet-inducible counterpart reverse tTA, and about one fourth of these are reported to have transgene expression in the brain[14]
Comparison of expression patterns reported across the myriad tTA/reverse tTA (rtTA) lines has historically been difficult because of the varying methods used to locate transgene expression compounded by significant variation in spatial granularity and scope of analyses
Summary
Transgenic mice in which the expression of specific genes can be pharmacologically regulated are powerful tools for studying brain disease[1,2,3,4,5,6,7,8,9,10]. These studies have mapped reporter expression in tTA driver lines based on the promoters for cellular prion protein (Prnp)[4], neuropeptide Y receptors Y1 and Y520, Ca2+/calmodulin-dependent protein kinase IIα (Camk2a)[21], and neuropsin (Nop)[22] Three of these studies provide web-based virtual microscopy and repositories with series of histological section images spanning the mouse brain. A subset of corresponding sections can be compared side-by-side, as shown by Odeh et al.[21] To overcome this limitation in cross-model comparison, we present a repository of serial microscopic images showing lacZ reporter activity in five frequently used tTA-expressing transgenic lines (Prnp; Camk2a; Nop; L7/Purkinje cell protein 2, Pcp[2]; and Pituitary homeobox 3, Pitx[3]). The image repository is suitable as a benchmark reference for transgenic mouse models with tetracycline-controlled transgene expression in the brain
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