title: Expression mapping of tetracycline-responsive prion protein promoter: digital atlasing for generating cell-specific disease models.
abstract: We present a digital atlas system that allows mapping of molecular expression patterns at cellular resolution through large series of histological sections. Using this system, we have mapped the distribution of a distinct marker, encoded by the LacZ reporter gene driven by the tetracycline-responsive prion protein promoter in double transgenic mice. The purpose is to evaluate the suitability of this promoter mouse line for targeting genes of interest to specific brain regions, essential for construction of inducible transgenic disease models. Following processing to visualize the promoter expression, sections were counterstained to simultaneously display cytoarchitectonics. High-resolution mosaic images covering entire coronal sections were collected through the mouse brain at intervals of 200 microm. A web-based application provides access to a customized virtual microscopy tool for viewing and navigation within and across the section images. For each section image, the nearest section in a standard atlas is defined, and annotations of key structures and regions inserted. Putative categorization of labeled cells was performed with use of distribution patterns, followed by cell size and shape, as parameters that were compared to legacy data. Among the ensuing results were expression of this promoter in putative glial cells in the cerebellum (and not in Purkinje cells), in putative glial cells in the substantia nigra, in pallidal glial cells or interneurons, and in distinct cell layers and regions of the hippocampus. The study serves as a precursor for a database resource allowing evaluation of the suitability of different promoter mouse lines for generating disease models.
authors.affiliation: Department of Medical Genetics, University of Tübingen, Tübingen, Germany.
authors.forename: Jana
authors.initials: J
authors.lastname: Boy
authors.forename: Trygve B
authors.initials: TB
authors.lastname: Leergaard
authors.forename: Thorsten
authors.initials: T
authors.lastname: Schmidt
authors.forename: Francis
authors.initials: F
authors.lastname: Odeh
authors.forename: Ulrike
authors.initials: U
authors.lastname: Bichelmeier
authors.forename: Silke
authors.initials: S
authors.lastname: Nuber
authors.forename: Carsten
authors.initials: C
authors.lastname: Holzmann
authors.forename: Andreas
authors.initials: A
authors.lastname: Wree
authors.forename: Stanley B
authors.initials: SB
authors.lastname: Prusiner
authors.forename: Hermann
authors.initials: H
authors.lastname: Bujard
authors.forename: Olaf
authors.initials: O
authors.lastname: Riess
authors.forename: Jan G
authors.initials: JG
authors.lastname: Bjaalie
mesh_terms: D000818:Animals; D001331:Automation; D001921:Brain / Q000033:anatomy & histology* / Q000166:cytology / Q000473:pathology; D001931:Brain Mapping / Q000379:methods*; D002531:Cerebellum / Q000502:physiology; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008853:Microscopy; D011328:Prions / Q000235:genetics*; D011401:Promoter Regions, Genetic; D013378:Substantia Nigra / Q000502:physiology; D014584:User-Computer Interface; D001616:beta-Galactosidase / Q000235:genetics
chemical_list: D011328:Prions; D001616:beta-Galactosidase