Each of the three PROJECTS in this Program will explore the cellular, molecular, and physiological mechanisms that underlie pediatric dysphagia in 22q11 Deletion Syndrome (22q11DS), using the LgDel mouse, which is an accurate genetic model of the human disorder, as well as related compound mutants and transgenics. CORE B, Animal Models and Dysphagia Pathology, will facilitate completion of all of the Specific Aims of these PROJECTS by providing a reliable and consistent supply of thoroughly characterized mouse models on a well-characterized single genetic background across all PROJECTS. CORE B will provide standardized genotyping and documentation, training and consultation for PROJECT personnel on working with mouse models. By centralizing these services, we can ensure the consistency and fidelity of each of the mouse models across PROJECTS. CORE B also will work with PROJECTS 1 and 3 to perform standardized assessment of feeding and swallowing, including acute feeding assays and the analysis of the respiratory pathology resulting from dysphagia. By utilizing a uniform approach to each of these assays, we will ensure that data from each PROJECT's aims are directly comparable to parallel experiments performed in other aims by other PROJECT personnel. This will enhance the precise and rigorous integration and management of genotypic and phenotypic data across PROJECTs in line with the NINDS ?Pre-clinical Rigor? guidelines, prevent significant duplication of effort, and maximize the investment of Program resources. Consolidation of the generation and phenotypic analysis of mouse models of dysphagia in CORE B will allow each research group to focus on key analytic approaches that are their specialties, rather than investing significant time, training, and effort in the genetic strategies necessary to generate crosses, follow compound genotypes, and obtain sufficient numbers of experimental animals for rigorous analysis. In addition, we will facilitate phenotypic assessment of dysphagia, and ensure that phenotypic measures obtained by each PROJECT can be compared qualitatively and quantitatively to one another. Together, the services, facilities, and training provided by CORE B will enhance the research productivity and quality of each of the three PROJECTS. These Core services will result in significant time and cost savings, and permit PROJECT investigators and laboratories to focus on their research specialties, with ready access to high-quality animal models and phenotypic assessment of dysphagia. NARRATIVE CORE B, Animal Models and Dysphagia Pathology will provide high-quality genetic mouse models of the human 22q11 Deletion Syndrome that will be used by all three PROJECTS in the Program. Because children with this neurodevelopmental disability have significant difficulties feeding and swallowing, CORE B will facilitate the accurate phenotypic assessment of mice that display these same problems. As a centralized Core facility, we can provide these services with a high level of reproducibility that ensures standardization across the PROJECTS, minimizes bias and prevents duplication of effort to conserve Program resources.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Research Program Projects (P01)
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Pediatrics Subcommittee (CHHD-A)
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George Washington University
Domestic Higher Education
United States
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Wang, Xin; Bryan, Corey; LaMantia, Anthony-Samuel et al. (2017) Altered neurobiological function of brainstem hypoglossal neurons in DiGeorge/22q11.2 Deletion Syndrome. Neuroscience 359:1-7
Karpinski, Beverly A; Bryan, Corey A; Paronett, Elizabeth M et al. (2016) A cellular and molecular mosaic establishes growth and differentiation states for cranial sensory neurons. Dev Biol 415:228-241
Baker, Jennifer L; Wood, Bernard; Karpinski, Beverly A et al. (2016) Testicular receptor 2, Nr2c1, is associated with stem cells in the developing olfactory epithelium and other cranial sensory and skeletal structures. Gene Expr Patterns 20:71-9
LaMantia, Anthony-Samuel; Moody, Sally A; Maynard, Thomas M et al. (2016) Hard to swallow: Developmental biological insights into pediatric dysphagia. Dev Biol 409:329-42
Meechan, Daniel W; Maynard, Thomas M; Tucker, Eric S et al. (2015) Modeling a model: Mouse genetics, 22q11.2 Deletion Syndrome, and disorders of cortical circuit development. Prog Neurobiol 130:1-28
Paronett, Elizabeth M; Meechan, Daniel W; Karpinski, Beverly A et al. (2015) Ranbp1, Deleted in DiGeorge/22q11.2 Deletion Syndrome, is a Microcephaly Gene That Selectively Disrupts Layer 2/3 Cortical Projection Neuron Generation. Cereb Cortex 25:3977-93