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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    • "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.
    Mammalian Genome 06/2015; 26(7-8). DOI:10.1007/s00335-015-9571-1 · 3.07 Impact Factor
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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.
    Development 11/2014; 141(22):4254-66. DOI:10.1242/dev.115436 · 6.46 Impact Factor
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    • "Heterozygous Fcgr4-null mice were received from the European Conditional Mouse Mutagenesis Program consortia distributed by the Helmholtz Zentrum München, Munich, Germany. The original ES cell containing the targeting construct was developed by the international mouse knockout consortium resulting in a non-conditional deletion of the Fcgr4 gene and were initially supplied on the mixed C57BL/6;129S5/SvEvBrd background [19]. Deletion was confirmed by genomic PCR before crossing back onto the C57BL/6 background for at least 10 generations and inter-crossing to generate homozygous knock-out mice. "
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    ABSTRACT: Anti-glycan/ganglioside antibodies are the most common immune effectors found in patients with Guillain-Barré Syndrome, which is a peripheral autoimmune neuropathy. We previously reported that disease-relevant anti-glycan autoantibodies inhibited axon regeneration, which echo the clinical association of these antibodies and poor recovery in Guillain-Barré Syndrome. However, the specific molecular and cellular elements involved in this antibody-mediated inhibition of axon regeneration are not previously defined. This study examined the role of Fcγ receptors and macrophages in the antibody-mediated inhibition of axon regeneration. A well characterized antibody passive transfer sciatic nerve crush and transplant models were used to study the anti-ganglioside antibody-mediated inhibition of axon regeneration in wild type and various mutant and transgenic mice with altered expression of specific Fcγ receptors and macrophage/microglia populations. Outcome measures included behavior, electrophysiology, morphometry, immunocytochemistry, quantitative real-time PCR, and western blotting. We demonstrate that the presence of autoantibodies, directed against neuronal/axonal cell surface gangliosides, in the injured mammalian peripheral nerves switch the proregenerative inflammatory environment to growth inhibitory milieu by engaging specific activating Fcγ receptors on recruited monocyte-derived macrophages to cause severe inhibition of axon regeneration. Our data demonstrate that the antibody orchestrated Fcγ receptor-mediated switch in inflammation is one mechanism underlying inhibition of axon regeneration. These findings have clinical implications for nerve repair and recovery in antibody-mediated immune neuropathies. Our results add to the complexity of axon regeneration in injured peripheral and central nervous systems as adverse effects of B cells and autoantibodies on neural injury and repair are increasingly recognized.
    PLoS ONE 02/2014; 9(2):e88703. DOI:10.1371/journal.pone.0088703 · 3.23 Impact Factor
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