The broad goal of the Disease Model Unit (DMU) is to support the generation of new mouse models of human disease in The Jackson Laboratory (JAX) Center for Precision Genetics (JCPG) by providing the facilities and expertise for model-generation pipelines. New models will be generated for six categories of human disease in six separate research projects in the DMU: epileptic encephalopathy, type I diabetes, age-related macular degeneration, chronic kidney disease, Charcot-Marie-Tooth disease, and amyotrophic lateral sclerosis. Model generation will be supported by both leveraging and further specializing the facilities and expertise in existing Scientific Service cores at JAX. Three new cores will be carved out of existing JAX Services: The Genome Editing Core will provide tools for precise genetic engineering; the Behavioral Phenotyping Core will support neurological disease model characterization; and the Viral Vector Custom Design Core will provide Center investigators with custom viral vectors for gene delivery and gene knock-down studies. Other JAX Services will be used that are already sufficiently appropriate and outfitted for the DMU pipeline. While each DMU project will develop its own disease-specific pipeline for model generation, all of them will be supported by the coordination of core resources and expertise provided through the DMU.
The Specific Aims of the DMU are: 1) To demonstrate capacity over a range of human conditions, organ systems and ages; 2) to examine common and rare disease; 3) to integrate and fine-tune technologies to the needs of individual research projects, while retaining central efficiency of scale; 4) to emphasize new assays for throughput and efficiency, without losing sight of disease in a native organ system or the intact animal; and 5) to recognize and overcome interspecies differences that are obstacles to further progress. Together with the Center's other major Cores, the DMU- supported pipelines will provide project investigators with the resources and expertise that will ensure generation of models ready for preclinical testing.
|Presa, Maximiliano; Racine, Jeremy J; Dwyer, Jennifer R et al. (2018) A Hypermorphic Nfkbid Allele Contributes to Impaired Thymic Deletion of Autoreactive Diabetogenic CD8+ T Cells in NOD Mice. J Immunol 201:1907-1917|
|Schloss, Jennifer; Ali, Riyasat; Racine, Jeremy J et al. (2018) HLA-B*39:06 Efficiently Mediates Type 1 Diabetes in a Mouse Model Incorporating Reduced Thymic Insulin Expression. J Immunol 200:3353-3363|
|Racine, Jeremy J; Stewart, Isabel; Ratiu, Jeremy et al. (2018) Improved Murine MHC-Deficient HLA Transgenic NOD Mouse Models for Type 1 Diabetes Therapy Development. Diabetes 67:923-935|
|Ratiu, Jeremy J; Racine, Jeremy J; Hasham, Muneer G et al. (2017) Genetic and Small Molecule Disruption of the AID/RAD51 Axis Similarly Protects Nonobese Diabetic Mice from Type 1 Diabetes through Expansion of Regulatory B Lymphocytes. J Immunol 198:4255-4267|
|Morelli, Kathryn H; Seburn, Kevin L; Schroeder, David G et al. (2017) Severity of Demyelinating and Axonal Neuropathy Mouse Models Is Modified by Genes Affecting Structure and Function of Peripheral Nodes. Cell Rep 18:3178-3191|
|Chiang, Wei-Chieh; Chan, Priscilla; Wissinger, Bernd et al. (2017) Achromatopsia mutations target sequential steps of ATF6 activation. Proc Natl Acad Sci U S A 114:400-405|
|Tian, Cong; Gagnon, Leona H; Longo-Guess, Chantal et al. (2017) Hearing loss without overt metabolic acidosis in ATP6V1B1 deficient MRL mice, a new genetic model for non-syndromic deafness with enlarged vestibular aqueducts. Hum Mol Genet 26:3722-3735|
|Korstanje, Ron; Ryan, Jennifer L; Savage, Holly S et al. (2017) Continuous Glucose Monitoring in Female NOD Mice Reveals Daily Rhythms and a Negative Correlation With Body Temperature. Endocrinology 158:2707-2712|
|Snyder, Elizabeth M; McCarty, Christopher; Mehalow, Adrienne et al. (2017) APOBEC1 complementation factor (A1CF) is dispensable for C-to-U RNA editing in vivo. RNA 23:457-465|
|Wang, Qiming; Racine, Jeremy J; Ratiu, Jeremy J et al. (2017) Transient BAFF Blockade Inhibits Type 1 Diabetes Development in Nonobese Diabetic Mice by Enriching Immunoregulatory B Lymphocytes Sensitive to Deletion by Anti-CD20 Cotherapy. J Immunol 199:3757-3770|
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