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Here we report the isolation of a murine model for heritable T cell lymphoblastic leukemia/lymphoma (T-ALL) called Spontaneous dominant leukemia (Sdl). Sdl heterozygous mice develop disease with a short latency and high penetrance, while mice homozygous for the mutation die early during embryonic development. Sdl mice exhibit an increase in the frequency of micronucleated reticulocytes, and T-ALLs from Sdl mice harbor small amplifications and deletions, including activating deletions at the Notch1 locus. Using exome sequencing it was determined that Sdl mice harbor a spontaneously acquired mutation in Mcm4 (Mcm4(D573H)). MCM4 is part of the heterohexameric complex of MCM2-7 that is important for licensing of DNA origins prior to S phase and also serves as the core of the replicative helicase that unwinds DNA at replication forks. Previous studies in murine models have discovered that genetic reductions of MCM complex levels promote tumor formation by causing genomic instability. However, Sdl mice possess normal levels of Mcms, and there is no evidence for loss-of-heterozygosity at the Mcm4 locus in Sdl leukemias. Studies in Saccharomyces cerevisiae indicate that the Sdl mutation produces a biologically inactive helicase. Together, these data support a model in which chromosomal abnormalities in Sdl mice result from the ability of MCM4(D573H) to incorporate into MCM complexes and render them inactive. Our studies indicate that dominantly acting alleles of MCMs can be compatible with viability but have dramatic oncogenic consequences by causing chromosomal abnormalities.
Pubmed ID: 23133403 RIS Download
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Integrated database resource consisting of 16 main databases, broadly categorized into systems information, genomic information, and chemical information. In particular, gene catalogs in completely sequenced genomes are linked to higher-level systemic functions of cell, organism, and ecosystem. Analysis tools are also available. KEGG may be used as reference knowledge base for biological interpretation of large-scale datasets generated by sequencing and other high-throughput experimental technologies.
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These Brainbow 1.0 (founder line L) mice allow labeling of individual neuronal types (specifically hippocampal neuron cell bodies, and including motor neurons, dentate gyrus granule cells, pyramidal neurons of the cortex and CA1 area) with approximately 166 distinguishable color variations in cre recombined cells, and may also be useful in conjunction with other Brainbow strains (Stock No. 007901, Stock No. 007911, Stock No. 007921) for neurobiological studies. These Thy1-Brainbow 1.0 (line L) transgenic mice are viable and fertile. The mice possess multiple fluorescent protein sequences uniquely flanked with pairs of incompatible Lox sites alternated to create mutually exclusive recombination events; allowing stochastic expression of multiple fluorescent proteins from a single transgene. Prior to Cre-mediated recombination, the fluorescent protein immediately adjacent to the promoter, dTomato (RFP), is expressed in peripheral and central neurons. When bred to Cre recombinase expressing mice, the resulting offspring can have one of three expression outcomes for each transgene in each cell of the cre expressing tissue(s): dTomato (RFP) (no recombination), mCerulean (CFP), or mYFP. Integration of tandem transgene copies yields combinatorial fluorescent protein expression in each cell, and thus many possible cell colors, providing a way to distinguish adjacent neurons and visualize other cellular interactions. Of note, the single FRT site inserted in the transgene allows tandem transgene copy number reduction through Flp-mediated recombination if desired. These Brainbow 1.0 (founder line L) mice were found to have multiple transgene copies that allow labeling of individual neuronal types (specifically hippocampal neuron cell bodies, and including motor neurons, dentate gyrus granule cells, pyramidal neurons of the cortex and CA1 area) with approximately 166 distinguishable color variations in cre recombined cells, and may also be useful in conjunction with other Brainbow strains (Stock No. 007901, Stock No. 007911, Stock No. 007921) for neurobiological studies. This mouse can be used to support research in many areas including:
Neurobiology Research
* Cre-lox System (loxP-flanked Sequences)
* Fluorescent protein expression in neural tissue
Research Tools
* Cre-lox-System (loxP-flanked Sequences: Test/Reporter)
* Developmental Biology Research (Cre-lox system)
* Developmental Biology Research (transplantation marker for embryonic and adult tissue)
* FLP-FRT System (FRT-flanked Sequences)
* Fluorescent Proteins * Genetics Research (Mutagenesis and Transgenesis: Cre-lox system) * Genetics Research (Tissue/Cell Markers: Cre-lox system) * Genetics Research (Tissue/Cell Markers: astrocyte-specific marker) * Genetics Research (Tissue/Cell Markers: astrocytes) * Genetics Research (Tissue/Cell Markers: astrocytes, neurons) * Genetics Research (Tissue/Cell Markers: glial cells) * Genetics Research (Tissue/Cell Markers: multiple) * Genetics Research (Tissue/Cell Markers: neurons) * Genetics Research (Tissue/Cell Markers: transplantation marker for embryonic and adult tissue) * Neurobiology Research (astrocyte-specific marker) * Neurobiology Research (cell marker) * YFP related Research Tools * Fluorescent Proteins Control: 000664 C57BL/6J (approximate)
Mus musculus with name 129S1/SvImJ from IMSR.
View all literature mentionsMus musculus with name FVB/NJ from IMSR.
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
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