The histology and stereology support core was created to maximize the use of available resources for mouse brain tissue processing, paraffin or cryo- embedding, serial sectioning and histological staining of sections for stereology and collaborative studies involving Projects 1, 2, 3 and 4. Core B also provides equipment, supplies and expertise required for the processing, embedding, sectioning and histological staining of brain tissue from patients ascertained through the Director and clinical collaborators. The goals of Core B include: 1. Preparation of tissue and standardization of stereological methods in adult and postnatal brain of genetic mouse models. For all models in the PPG the core will produce material facilitating the direct comparison of mouse strains using highly standardized histological and quantitative anatomical methods. 2. Whole-brain phenotyping of models. Brains will be paraffin-embedded at key postnatal ages for phenotyping with histochemical (H&E/NissI) and immunological stains. Data will include sizes of major nuclei;total cell number and pathological cell profiles. Projection neuron representation will be assessed by cell morphology and immunohistochemistry (IHC). 3. Archiving brains of behaviorally characterized mice. The time and resources invested in behavioral testing makes it cost effective to paraffin embed and archive all brains from behavioral studies. These tissues can be used to confirm an anatomical effect in the same cohort or test posf hoc hypotheses related to known behavioral phenotypes. 4. Archiving embryos (some BrdU pulse-labeled) of multiple genotypes at a range of gestational ages. Extra embryos generated by Projects 1,2 &3 experiments will be processed, paraffin embedded and archived to be available for later investigation of new questions and hypotheses as the work progresses. 5. Correlative human brain pathology. While rodent models suggest that human disorders affecting primarily interneurons are likely, human data are mostly lacking. Core B will process tissue blocks or fixed tissues ascertained through the Director and clinical collaborators. Slides prepared for histochemistry and IHC in Core B will be analyzed by Project 1 and 2 investigators. 6. Mouse inventory and identification. Although each project will maintain its own mouse lines, Core B, will periodically update the nomenclature and inventory of genetic models available through the PPG and facilitate coordination across projects in order to procure and facilitate initial analysis of useful lines and crosses.
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