Large scale international activities for systematic conditional mouse mutagenesis, exploiting advances in the sophisticated manipulation of the mouse genome, has established the mouse as the premier organism for developing models of human disease and drug action. Conditional mutagenesis is critical for the elucidation of the gene functions that exert pleiotropic effects in a variety of cell types and tissues throughout the life of the animal. The majority of new mouse mutants are therefore designed as conditional, activated only in a specific tissue (spatial control) and/or life stage (temporal control) through biogenic Cre/loxP technologies. The full power of conditional mutant mice can therefore only be exploited with the availability of well characterized mouse lines expressing Cre-recombinase in tissue, organ and cell type-specific patterns, to allow the creation of somatic mutations in defined genes. This chapter provides an update on the current state of Cre driver mouse lines worldwide, and reviews the available public databases and portals that capture critical details of Cre driver lines such as the efficiency of recombination, cell tissue specificity, or genetic background effects. The continuously changing landscape of these mouse resources reflects the rapid progression of research and development in conditional and inducible mouse mutagenesis.
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Embryonic stem cell distribution unit that distributes material arising within European Conditional Mouse Mutagenesis Program consortium, currently targeting vectors and ES cells. Upon user request EUCOMM grow targeting vectors from glycerol stocks and prepare vector DNA. Identity of vector is verified by restriction mapping. Upon user request EUCOMM thaw, expand and re-freeze several aliquots of desired ES cell clone. Standard controls include PCR based assay. Upon additional request EuMMCR unit develops genotyping PCR, which can be used to genotype chimeric mice that may be generated using those ES cell clones.
View all literature mentionsGlobal nonprofit biological resource center (BRC) and research organization that provides biological products, technical services and educational programs to private industry, government and academic organizations. Its mission is to acquire, authenticate, preserve, develop and distribute biological materials, information, technology, intellectual property and standards for the advancement and application of scientific knowledge. The primary purpose of ATCC is to use its resources and experience as a BRC to become the world leader in standard biological reference materials management, intellectual property resource management and translational research as applied to biomaterial development, standardization and certification. ATCC characterizes cell lines, bacteria, viruses, fungi and protozoa, as well as develops and evaluates assays and techniques for validating research resources and preserving and distributing biological materials to the public and private sector research communities.
View all literature mentionsProject to provide Neuroscience Community with mouse strains that are suitable for tissue and cell-type-specific perturbation of gene function in nervous system. NIH Neuroscience Blueprint has established three centers in the USA for generation of genetically modified mice expressing CRE recombinases in nervous system on the C57BJ/6 genetic background. Mouse lines are generated at Cold Spring Harbor Lab, at Scripps Research Institute, and at Baylor College of Medicine.
View all literature mentionsGene expression data and maps of mouse central nervous system. Gene expression atlas of developing adult central nervous system in mouse, using in situ hybridization and transgenic mouse techniques. Collection of pictorial gene expression maps of brain and spinal cord of mouse. Provides tools to catalog, map, and electrophysiologically record individual cells. Application of Cre recombinase technologies allows for cell-specific gene manipulation. Transgenic mice created by this project are available to scientific community.
View all literature mentionsNational public repository system for mutant mice. Archives and distributes scientifically valuable spontaneous and induced mutant mouse strains and ES cell lines for use by biomedical research community. Includes breeding/distribution facilities and information coordinating center. Mice strains are cryopreserved, unless live colony must be established. Live mice are supplied from production colony, from colony recovered from cryopreservation, or via micro-injection of cell line into host blastocysts. MMRRC member facilities also develop technologies to improve handling of mutant mice, including advances in assisted reproductive techniques, cryobiology, genetic analysis, phenotyping and infectious disease diagnostics.
View all literature mentionsA comprehensive characterization of expression patterns of genetically-controlled markers or tool genes in the brains of transgenic mice generated by the Allen Institute as well as the broad scientific community. Providing standardized, detailed, anatomical profiling of transgene expression throughout the brain, this dataset is intended to reveal the potential of each transgenic mouse line and help researchers choose the appropriate tools for their studies. Transgenic mice are valuable tools to label selective neuronal or non-neuronal populations, modulate gene expression in these cells or manipulate activity of these cells for the study of neural circuits and brain function. The Allen Institute has launched a project to generate a variety of transgenic mouse lines, mainly using the Cre/lox system, to express fluorescent probes or neuronal activity manipulating tools in a variety of cell types in the brain. At the same time, utilizing Allen Institute's unique high-throughput capability, a pipeline is set up to characterize the ability in directing cell type specific expression in the brains of various transgenic mice generated by the Allen Institute as well as the broad scientific community. Through standardized, detailed, anatomical profiling of the transgene expression in the entire mouse brain, this dataset is intended to provide a comprehensive evaluation of the potential of each transgenic mouse line and help researchers choose the appropriate transgenic tools to study the function of different regions and/or cell types of the brain. This data release adds additional data to the existing set of new Cre-reporter lines generated at the Allen Institute that have stronger expression than other commonly used reporter lines are used to characterize approximately a dozen Cre-driver lines. The types of characterization data include digitized images (of sections sampling the entire brain) of colorimetric in situ hybridization (CISH), double fluorescent in situ hybridization (DFISH), native fluorescence of XFP (generic term for fluorescent proteins of different colors), and immunohistochemical (IHC) labeling of marker genes.
View all literature mentionsGenerate, archive, and distribute world-wide up to 12.000 conditional mutations across the mouse genome in mouse embryonic stem (ES) cells and Establish a limited number of mouse mutants from this resource. EUCOMM contributes the largest fraction of conditionally trapped and targeted genes in mouse C57BL/6N embryonic stem (ES) cells to the IKMC. EUCOMM vectors, mutant ES cells and mutant mice are distributed worldwide, enabling functional genomics research in a standardized and cost-effective manner by a much wider biomedical research community than has been possible previously. EUCOMM mutant ES cells and vectors can be obtained from the European Mouse Mutant Cell Repository (EuMMCR). EUCOMM mutant mice are archived and distributed by the European Mouse Mutant Archive (EMMA). Mutagenesis Strategies * Conditional gene trapping - random approach for expressed genes * Conditional targeted trapping - directed approach, used for expressed genes * Conditional gene targeting - directed approach, used for non-expressed genes
View all literature mentionsProject to generate human DNA promoters of less than 4 kb (MiniPromoters) to drive gene expression in defined brain regions of therapeutic interest for diseases such as Alzheimer, Parkinson, Huntington, Amyotrophic Lateral Sclerosis, Multiple Sclerosis, Spinocerebellar Ataxia, Depression, Autism, and Cancer. Project develops and shares tools like human MiniPromoters that drive region- and cell-specific gene expression in the mouse brain, expression constructs, mouse embryonic stem cell lines, and knock-in mice all of which carry brain-specific MiniPromoters. Project is daughter of Genome Canada Project, Atlas of Gene Expression in Mouse Development, within which mouse brain gene expression data have already been gathered. Project team has collaborated with International BioPharma Solutions Ltd., management and communications consulting company specializing in product development and commercialization advice. Project will explore challenging interface between science and journalism with focus on genomics and gene therapy.
View all literature mentionsAn independent, nonprofit organization focused on mammalian genetics research to advance human health. Their mission is to discover the genetic basis for preventing, treating, and curing human disease, and to enable research for the global biomedical community. Jackson Laboratory breeds and manages colonies of mice as resources for other research institutions and laboratories, along with providing software and techniques. Jackson Lab also conducts genetic research and provides educational material for various educational levels.
View all literature mentionsRepository of Cre Driver lines and related information resources. Their services include analysis of Cre line excision function in both target and non-target tissues using Cre reporter lines and presenting the annotated data in the expression data portion of this website, http://cre.jax.org/data.html.
View all literature mentionsDatabase of the international consortium working together to mutate all protein-coding genes in the mouse using a combination of gene trapping and gene targeting in C57BL/6 mouse embryonic stem (ES) cells. Detailed information on targeted genes is available. The IKMC includes the following programs: * Knockout Mouse Project (KOMP) (USA) ** CSD, a collaborative team at the Children''''s Hospital Oakland Research Institute (CHORI), the Wellcome Trust Sanger Institute and the University of California at Davis School of Veterinary Medicine , led by Pieter deJong, Ph.D., CHORI, along with K. C. Kent Lloyd, D.V.M., Ph.D., UC Davis; and Allan Bradley, Ph.D. FRS, and William Skarnes, Ph.D., at the Wellcome Trust Sanger Institute. ** Regeneron, a team at the VelociGene division of Regeneron Pharmaceuticals, Inc., led by David Valenzuela, Ph.D. and George D. Yancopoulos, M.D., Ph.D. * European Conditional Mouse Mutagenesis Program (EUCOMM) (Europe) * North American Conditional Mouse Mutagenesis Project (NorCOMM) (Canada) * Texas A&M Institute for Genomic Medicine (TIGM) (USA) Products (vectors, mice, ES cell lines) may be ordered from the above programs.
View all literature mentionsThe CREATE consortium represents a core of major European and international mouse database holders and research groups involved in conditional mutagenesis, primarily to develop a strategy for the integration and dissemination of Cre driver strains for modelling aspects of complex human diseases in the mouse. Collectively the participants have amassed a significant number of these strains in their respective databases. Therefore one of the goals of CREATE is to provide a unified portal for worldwide access to these critical resources. The portal can either be searched through an advanced BioMart interface, by driver name, or by anatomical site of expression using Embryonic Mouse Anatomy Project (EMAP) and Mouse Anatomy (MA) ontology terms. Search results link back to the original source of the data for more detailed information and to IMSR to order mice if available. The ontology browser is particularly useful as it enables the CREATE consortium to identify cell and tissues that are not currently covered by existing lines. CREATE also aims to coordinate the production of suitable lines by the Cre generation projects described above. Through the CREATE portal, the CREATE consortium aims to develop a strategy for the production, integration and dissemination of new Cre driver strains for modelling aspects of complex human diseases in the mouse. CREATE is also developing a roadmap for harnessing emerging technologies and methods for improving Cre-mediated recombination in vivo through targeted, intensive workshops and discussion forums on the portal. This will entail review of construct design options for classical transgenic constructs (promoter/enhancer used, small size <2025 Kb) vs large transgenic constructs (BAC, P1, YAC etc.); methods used for Cre transgenic lines including random vs targeted integration, position independent expression loci, or replacement of endogenous coding sequences with Cre recombinase under the control of the endogenous locus. CREATE provides a platform for discussion of additional issues specific to inducible Cre strategies including background activity before induction, inducibility (kinetics), efficiency, and protocols used for induction of Cre recombinase activity. Additional components of the technology roadmap will be the cataloguing of other existing methodologies (rtTA, FLP, Dre) of mouse genome modification, sharing information on validated Cre mutant lines as well as identification and assessment of new methods of mutagenesis such as RNAi and other emerging technologies. Other discussion topics addressed through surveys on the CREATE portal include the characterization of Cre lines (specificity of expression/deletion; efficiency of expression/ deletion; reproducibility of deletion from animal to animal for the same floxed allele; reproducibility with different floxed alleles; timing of expression/deletion, etc.), the extent to which Cre expression changes upon backcrossing to specific genetic backgrounds through variegation and silencing; potential phenotypes caused by either integration- mediated mutagenesis or Cre ''toxicity''; and other factors affecting the specificity of Cre-mediated expression/deletion. CREATE regularly integrates common fields from the Cre-X, CreZOO and the MGI recombinase portal resources described below. The data in common consists of: * Transgene or Knock-in name. * MGI ID of allele. * Driver. * Anatomical site of expression. * Pubmed ID. * IMSR strain name and link. * Inducibility (YES/NO).
View all literature mentionsCentral repository for the physical archive and distribution of cryopreserved ES cells, spermatozoa, ova, embryos, and non-germ cell tissue DNA generated by Canada''''s mouse genome effort. The CMMR acts in coordination with other repositories worldwide and is establishing a nation-wide network of repository nodes to house sub-sets of the resources generated across Canada. The CMMR is the repository and distribution center for the North American Conditional Mouse Mutagenesis project (NorCOMM). The CMMR also collects and stores somatic tissue from mouse models in a variety of formats (fixed, embedded, and glass-slide mounted) enabling world wide access to specimens from established mouse models. Services include: * Embryo cryopreservation and recovery * Ovary cryopreservation and recovery * Ovary transplant * Sperm cryopreservation and recovery * Strain services, including rederivation by IVF, speed expansion and strain rescue * NorCOMM ES cell withdrawal * Non-NorCOMM ES cell expansion
View all literature mentionsSeattle based independent, nonprofit medical research organization dedicated to accelerating the understanding of how human brain works. Provides free data and tools to researchers and educators and variety of unique online public resources for exploring the nervous system. Integrates gene expression data and neuroanatomy, along with data search and viewing tools, these resources are openly accessible via the Allen Brain Atlas data portal. Provides Allen Mouse Brain, Allen Spinal Cord Atlas, Allen Developing Mouse Brain Atlas, Allen Human Brain Atlas,Allen Mouse Brain Connectivity Atlas, Allen Cell Type Database, The Ivy Glioblastoma Atlas Project (Ivy GAP), The BrainSpan Atlas of the Developing Human Brain.
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