A Mouse for All Reasons

Cell (Impact Factor: 32.24). 02/2007; 128(1):9-13. DOI: 10.1016/j.cell.2006.12.018
Source: PubMed


Three major mouse knockout programs are underway worldwide, working together to mutate all protein-encoding genes in the mouse using a combination of gene trapping and gene targeting in mouse embryonic stem (ES) cells. Although the current emphasis is on production of this valuable resource, there are significant efforts to facilitate program coordination, to enhance the availability of this resource, and to plan for future efforts in mouse genetics research.

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    • "Third, before the advent of next generation sequencing , attempts at saturation mutagenesis of the mouse genome with chemical mutagens were slow and expensive, requiring extensive breeding programmes to identify mutations [25]. Key research centres in the United States (US), continental Europe, the United Kingdom (UK), and Canada launched the IKMC effort, using gene targeting and, to lesser extent, gene trapping [26]. 1 The IKMC included the KnockOut Mouse Project (KOMP) funded by the National Institutes of Health (NIH, US), "
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    ABSTRACT: Bio-repositories and databases for biomedical research enable the efficient community-wide sharing of reagents and data. These archives play an increasingly prominent role in the generation and dissemination of bioresources and data essential for fundamental and translational research. Evidence suggests, however, that current funding and governance models, generally short-term and nationally focused, do not adequately support the role of archives in long-term, transnational endeavours to make and share high-impact resources. Our qualitative case study of the International Knockout Mouse Consortium and the International Mouse Phenotyping Consortium examines new governance mechanisms for archive sustainability. Funders and archive managers highlight in interviews that archives need stable public funding and new revenue-generation models to be sustainable. Sustainability also requires archives, journal publishers, and funders to implement appropriate incentives, associated metrics, and enforcement mechanisms to ensure that researchers use archives to deposit reagents and data to make them publicly accessible for academia and industry alike.
    Full-text · Article · Nov 2015 · New Biotechnology
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    • "The arrows highlight features that are present in gene predictions from Ensembl and HAVANA/Vega but not from NCBI genome features represented at NCBI's Gene resource (Brown et al. 2015; Sayers et al. 2012) and was a primary source of genes for the first phase of The International Knockout Mouse Project (KOMP) (Bradley et al. 2012; International Mouse Knockout et al. 2007). The output from MGI's unified gene catalog process systematically identifies gene models that are potentially problematic in their structural details as well as those that appear to be equivalent across different sources but have contradictory biotype annotations. "
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    ABSTRACT: We report here a semi-automated process by which mouse genome feature predictions and curated annotations (i.e., genes, pseudogenes, functional RNAs, etc.) from Ensembl, NCBI and Vertebrate Genome Annotation database (Vega) are reconciled with the genome features in the Mouse Genome Informatics (MGI) database ( into a comprehensive and non-redundant catalog. Our gene unification method employs an algorithm (fjoin—feature join) for efficient detection of genome coordinate overlaps among features represented in two annotation data sets. Following the analysis with fjoin, genome features are binned into six possible categories (1:1, 1:0, 0:1, 1:n, n:1, n:m) based on coordinate overlaps. These categories are subsequently prioritized for assessment of annotation equivalencies and differences. The version of the unified catalog reported here contains more than 59,000 entries, including 22,599 protein-coding coding genes, 12,455 pseudogenes, and 24,007 other feature types (e.g., microRNAs, lincRNAs, etc.). More than 23,000 of the entries in the MGI gene catalog have equivalent gene models in the annotation files obtained from NCBI, Vega, and Ensembl. 12,719 of the features are unique to NCBI relative to Ensembl/Vega; 11,957 are unique to Ensembl/Vega relative to NCBI, and 3095 are unique to MGI. More than 4000 genome features fall into categories that require manual inspection to resolve structural differences in the gene models from different annotation sources. Using the MGI unified gene catalog, researchers can easily generate a comprehensive report of mouse genome features from a single source and compare the details of gene and transcript structure using MGI’s mouse genome browser.
    Full-text · Article · Jun 2015 · Mammalian Genome
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    • "The identity of cells can be altered by the forced induction of combination of transcription factors (TFs) (Takahashi and Yamanaka, 2006; Vierbuchen et al., 2010; Ieda et al., 2010; Sekiya and Suzuki, 2011; Huang et al., 2011; Hiramatsu et al., 2011), the forced induction of single TFs (Davis et al., 1987; Nishiyama et al., 2009; Correa-Cerro et al., 2011; Yamamizu et al., 2013) or by the repression of single TFs (Skarnes et al., 2004; Ivanova et al., 2006; Collins et al., 2007; Nishiyama et al., 2013). "
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    ABSTRACT: Upon removal of culture conditions that maintain an undifferentiated state, mouse embryonic stem cells (ESCs) differentiate into various cell types. Differentiation can be facilitated by forced expression of certain transcription factors (TFs), each of which can generally specify a particular developmental lineage. We previously established 137 mouse ESC lines, each of which carried a doxycycline-controllable TF. Among them, Sox9 has unique capacity: its forced expression accelerates differentiation of mouse ESCs into cells of all three germ layers. With the additional use of specific culture conditions, overexpression of Sox9 facilitated the generation of endothelial cells, hepatocytes and neurons from ESCs. Furthermore, Sox9 action increases formation of p21 (WAF1/CIP1), which then binds to the SRR2 enhancer of pluripotency marker Sox2 and inhibits its expression. Knockdown of p21 abolishes inhibition of Sox2 and Sox9-accelerated differentiation, and reduction of Sox2 2 days after the beginning of ESC differentiation can comparably accelerate mouse ESC formation of cells of three germ layers. These data implicate the involvement of the p21-Sox2 pathway in the mechanism of accelerated ESC differentiation by Sox9 overexpression. The molecular cascade could be among the first steps to program ESC differentiation.
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