The Mouse Genetics Project (MGP) at the Wellcome Trust Sanger Institute aims to generate and phenotype over 800 genetically modified mouse lines over the next 5 years to gain a better understanding of mammalian gene function and provide an invaluable resource to the scientific community for follow-up studies. Phenotyping includes the generation of a standardized biobank of paraffin-embedded tissues for each mouse line, but histopathology is not routinely performed. In collaboration with the Pathology Core of the Centre for Modeling Human Disease (CMHD) we report the utility of histopathology in a high-throughput primary phenotyping screen. Histopathology was assessed in an unbiased selection of 50 mouse lines with (n=30) or without (n=20) clinical phenotypes detected by the standard MGP primary phenotyping screen. Our findings revealed that histopathology added correlating morphological data in 19 of 30 lines (63.3%) in which the primary screen detected a phenotype. In addition, seven of the 50 lines (14%) presented significant histopathology findings that were not associated with or predicted by the standard primary screen. Three of these seven lines had no clinical phenotype detected by the standard primary screen. Incidental and strain-associated background lesions were present in all mutant lines with good concordance to wild-type controls. These findings demonstrate the complementary and unique contribution of histopathology to high-throughput primary phenotyping of mutant mice.
Pubmed ID: 24652767 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
As one of three primary databases of PubChem (Pcsubstance, Pccompound, and PCBioAssay), PubChem Substance Database contains descriptions of chemical samples, from a variety of sources, and links to PubMed citations, protein 3D structures, and biological screening results that are available in PubChem BioAssay. If the contents of a chemical sample are known, the description includes links to PubChem Compound. A PubChem FTP is available and new data is accepted into the repository. Pcsubstance contains more than 81 million records (2011).
View all literature mentionsMultidisciplinary collaboration undertaking genome-wide mutagenesis to functionally annotate the mouse genome and develop new mouse models relevant to human disease. To achieve these goals two major research platforms are carried out: Gene trapping and ENU Mutagenesis. A new challenge is faced in the post-genomic era - the assignment of biological function to the human genome sequence and projecting that assignment into understanding of human health and disease. The Centre for Modeling Human Disease (CMHD) was established to take part in the worldwide initiative to address these challenges. At the CMHD, two fundamentally different, yet complimentary methods are employed to generate mutant mouse models of human disease: chemical mutagenesis by ethylnitrosourea (ENU), and gene trap insertional mutagenesis. The Centre contributes its resources to similar international efforts and is the first of its kind in Canada. The Center is also actively developing other mutagenic strategies including pharmacologic and genetic modifier screens to dissect disease pathways, and novel mutagenic techniques using embryonic stem cells. ENU Database * Statistics for Mouse Physiological Parameters * Search Mutants by Phenotype * Search Mutants by Heritability Gene Trap Database * Search by in vitro Expression Pattern * Search by Gene Trap Sequences CMHD Members Only (must register and login) * Search Mouse Line * Histopathology * Sperm, Tissue, Slide Archiving * CMHD Database Download CMHD Services * Phenotyping * Genetic Mapping * Pathology * Pathology Service Charges
View all literature mentionsCenter that produces knockout mice and carries out high-throughput phenotyping of each line in order to determine function of every gene in mouse genome. These mice will be preserved in repositories and made available to scientific community representing valuable resource for basic scientific research as well as generating new models for human diseases.
View all literature mentionsDatabase of mouse research resources at Sanger: BACs, targeting vectors, targeted ES cells, mutant mouse lines, and phenotypic data generated from the Institute''''s primary screen. The Wellcome Trust Sanger Institute generates, characterizes, and uses a variety of reagents for mouse genetics research. It also aims to facilitate the distribution of these resources to the external scientific community. Here, you will find unified access to the different resources available from the Institute or its collaborators. The resources include: 129S7 and C57BL6/J bacterial artificial chromosomes (BACs), MICER gene targeting vectors, knock-out first conditional-ready gene targeting vectors, embryonic stem (ES) cells with gene targeted mutations or with retroviral gene trap insertions, mutant mouse lines, and phenotypic data generated from the Institute''''s primary screen.
View all literature mentionsCommunity model organism database for laboratory mouse and authoritative source for phenotype and functional annotations of mouse genes. MGD includes complete catalog of mouse genes and genome features with integrated access to genetic, genomic and phenotypic information, all serving to further the use of the mouse as a model system for studying human biology and disease. MGD is a major component of the Mouse Genome Informatics.Contains standardized descriptions of mouse phenotypes, associations between mouse models and human genetic diseases, extensive integration of DNA and protein sequence data, normalized representation of genome and genome variant information. Data are obtained and integrated via manual curation of the biomedical literature, direct contributions from individual investigators and downloads from major informatics resource centers. MGD collaborates with the bioinformatics community on the development and use of biomedical ontologies such as the Gene Ontology (GO) and the Mammalian Phenotype (MP) Ontology.
View all literature mentions