Home About us Contact
|
Home About us Contact | ||
|
|
||
Mouse Gene (mouse + gene)
Kinds of Mouse Gene Selected AbstractsHumanizing a Mouse Gene for Human Therapeutics: Lessons From Denosumab,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 2 2009David Graham Little No abstract is available for this article. [source] Transcriptional profiling of a mice plague model: insights into interaction between Yersinia pestis and its hostJOURNAL OF BASIC MICROBIOLOGY, Issue 1 2009Haihong Liu Abstract Despite the importance of pneumonic plague caused by Yersinia pestis, a few is known about the interaction between Y. pestis and its host at the molecular level during the pneumonic plague development. In this study, we employed an intranasally challenged plague model in mice for investigating the kinetics of the disease progression by transcriptional profiling of Y. pestis and mice using qRT-PCR and microarray, respectively. The increasing transcription of important virulence genes of Y. pestis and of mice genes involving in immune and inflammatory defensive responses, and responses to stimuli, presents an overview of interaction between Y. pestis and mice during development of pneumonic plague. The early and persisting up-regulation of caf 1, psa A and lcr V in vivo indicated their role in resisting the host innate immune responses. The up-regulation of fur, ybt A and hms H in vivo reflected the ability of Y. pestis for acquiring iron. The transcription regulators, including pho P, oxy R and omp R, were up-regulated during plague development, suggesting their roles in interaction between Y. pestis and mice. Many genes encoding cytokines, such as IL2, IL-1B, CXCL2, CXCL5, CCL20, CD14 and TNFRSF13B, were up-regulated during the infection, confirming the report that they are important mediators to activate host responses to invading pathogens. The up-regulation of some genes encoding important virulent factors of Y. pestis and expression alterations of some genes encoding cytokines in the host reflect the interaction between the pathogen and the host, which will help us better understand plague pathogenesis. (© 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source] Targeted replacement of rodent CCR2 with the human orthologue CCR2B: A mouse model for in vivo analysis of human target-selective small molecule MCP-1 receptor antagonistsDRUG DEVELOPMENT RESEARCH, Issue 4 2002Haydn M. Prosser Abstract Rodent models for testing the efficacy of lead compounds are often invalidated by species selectivity of the compounds. The advent of mouse embryonic stem cell technology has allowed the development of genetically engineered mouse strains that incorporate a specific human gene in place of the orthologous mouse gene, a so-called knock-in mouse. This study describes the generation and validation of a mutant mouse line that expresses human CCR2B as a functional substitute for murine CCR2. The human CCR2B knock-in mice are viable and appear normal. In vitro assays indicate that the CCR2B knock-in is functionally expressed, giving a macrophage chemotactic profile in response to JE or MCP-1 that is similar to human peripheral blood monocytes rather than that of a murine macrophage cell line. In addition, the human selective CCR2B antagonist, SB-399721, was a more potent inhibitor of CCR2B knock-in macrophages in response to hMCP-1 than JE. The ability of the human CCR2B gene to functionally substitute for the mouse orthologue in vivo is demonstrated by a normal inflammatory response to intraperitoneal thioglycollate injection. Drug Dev. Res. 55:197,209, 2002. © 2002 Wiley-Liss, Inc. [source] Cloning, chromosomal localization and characterization of the murine mucin gene orthologous to human MUC4FEBS JOURNAL, Issue 13 2002Jean-Luc Desseyn We report here the full coding sequence of a novel mouse putative membrane-associated mucin containing three extracellular EGF-like motifs and a mucin-like domain consisting of at least 20 tandem repeats of 124,126 amino acids. Screening a cosmid and a BAC libraries allowed to isolate several genomic clones. Genomic and cDNA sequence comparisons showed that the gene consists of 25 exons and 24 introns covering a genomic region of ,,52 kb. The first intron is ,,16 kb in length and is followed by an unusually large exon (, 9.5 kb) encoding Ser/Thr-rich tandemly repeated sequences. Radiation hybrid mapping localized this new gene to a mouse region of chromosome 16, which is the orthologous region of human chromosome 3q29 encompassing the large membrane-anchored mucin MUC4. Contigs analysis of the Human Genome Project did not reveal any other mucin on chromosome 3q29 and, interestingly, our analysis allowed the determination of the genomic organization of the human MUC4 and showed that its exon/intron structure is identical to that of the mouse gene we cloned. Furthermore, the human MUC4 shares considerable homologies with the mouse gene. Based on these data, we concluded that we isolated the mouse ortholog of MUC4 we propose as Muc4. Expression studies showed that Muc4 is ubiquitous like SMC and MUC4, with highest levels of expression in trachea and intestinal tract. [source] Regulation of transcription of the Dnmt1 gene by Sp1 and Sp3 zinc finger proteinsFEBS JOURNAL, Issue 12 2002Shotaro Kishikawa The Sp family is a family of transcription factors that bind to cis -elements in the promoter regions of various genes. Regulation of transcription by Sp proteins is based on interactions between a GC-rich binding site (GGGCGG) in DNA and C-terminal zinc finger motifs in the proteins. In this study, we characterized the GC-rich promoter of the gene for the DNA methyltransferase (Dnmt1) that is responsible for methylation of cytosine residues in mammals and plays a role in gene silencing. We found that a cis -element (nucleotides ,161 to ,147) was essential for the expression of the mouse gene for Dnmt1. DNA-binding assays indicated that transcription factors Sp1 and Sp3 bound to the same cis -element in this region in a dose-dependent manner. In Drosophila SL2 cells, which lack the Sp family of transcription factors, forced expression of Sp1 or Sp3 enhanced transcription from the Dnmt1 promoter. Stimulation by Sp1 and Sp3 were independent phenomena. Furthermore, cotransfection reporter assays with a p300-expression plasmid revealed the activation of the promoter of the Dnmt1 gene in the presence of Sp3. The transcriptional coactivator p300 interacted with Sp3 in vivo and in vitro. Our results indicate that expression of the Dnmt1 gene is controled by Sp1 and Sp3 and that p300 is involved in the activation by Sp3. [source] A2-Pancortins (Pancortin-3 and -4) Are the Dominant Pancortins During Neocortical DevelopmentJOURNAL OF NEUROCHEMISTRY, Issue 1 2000Takashi Nagano We have identified a novel mouse gene named pancortin that is expressed dominantly in the mature cerebral cortex. This gene produces four different species of proteins, Pancortin-1-4, sharing a common region in the middle of their structure with two variations at the N-terminal (A1 or A2 part) and C-terminal (C1 or C2 part) sides, respectively. In the present study, we showed that expression of mRNAs for A2-Pancortins (Pancortin species that contain the A2 part, i.e., Pancortin-3 and -4) is more dominant than that of mRNAs for A1-Pancortins (Pancortin species that contain the A1 part, i.e., Pancortin-1 and -2) in the prenatal mouse cerebral neocortex. Using western blot analysis, we found that substantial amounts of both A2-Pancortins were present in the prenatal cerebral neocortex and P19 cells after inducing neuronal differentiation. A2-Pancortins were still present in the cerebral neocortex of the adult, although their mRNAs were hardly detected. In contrast, the amount of A1-Pancortins did not increase after the third postnatal week in spite of their intense gene expression. Furthermore, we showed that recombinant Pancortin-3, one of the A2-Pancortins, was a secreted protein, in contrast to Pancortin-1 (one of the A1-Pancortins). These results suggest that A2-Pancortins are extracellular proteins essential for neuronal differentiation and that their molecular behavior is distinct from that of A1-Pancortins. [source] Mice deficient for RNA-binding protein brunol1 show reduction of spermatogenesis but are fertileMOLECULAR REPRODUCTION & DEVELOPMENT, Issue 11 2007Arvind Dev Abstract RNA-binding proteins are involved in post-transcriptional processes like mRNA stabilization, alternative splicing, and transport. Brunol1 is a novel mouse gene related to elav/Bruno family of genes encoding for RNA-binding proteins. We report here the expression and functional analysis of murine Brunol1. Expression analysis of Brunol1 during embryogenesis by RT-PCR showed that Brunol1 expression starts at 9.5 dpc and continues to the later stages of embryonic development. In adult mice, the Brunol1 expression is restricted to brain and testis. We also analyzed the Brunol1 expression in testes of different mutants with spermatogenesis defects: W/WV, Tfm/y, Leyl,/,, olt/olt, and qk/qk. Brunol1 transcript was detectable in Leyl,/,, olt/olt, and qk/qk mutant but not in W/WV and Tfm/y mutants. We also showed by transfection of a fusion protein of green fluorescent protein and Brunol1 protein into NIH3T3 cells, that Brunol1 is localized in cytoplasm and nucleus. In order to elucidate the function of the Brunol1 protein in spermatogenesis, we disrupted the Brunol1 locus in mouse by homologous recombination, which resulted in a complete loss of the Brunol1 transcript. Male and female Brunol1+/, and Brunol1,/, mice from genetic backgrounds C57BL/6J,×,129/Sv hybrid and 129X1/SvJ when inbred exhibited normal phenotype and are fertile, although the number and motility of sperms are significantly reduced. An intensive phenotypic analysis showed no gross abnormalities in testis morphology. Collectively our results demonstrate that Brunol1 might be nonessential protein for mouse embryonic development and spermatogenesis. Mol. Reprod. Dev. 74: 1456,1464, 2007. © 2007 Wiley-Liss, Inc. [source] Molecular cloning and characterization of SRG-L, a novel mouse gene developmentally expressed in spermatogenic cellsMOLECULAR REPRODUCTION & DEVELOPMENT, Issue 9 2006Quanhong Ma Abstract Full-length cDNA of a novel mouse gene upregulated in late stages of spermatogenic cells was cloned from mouse testis using overlapping RT-PCR and RACE. The mRNA of the gene was expressed mainly in diplotene/pachytene spermatocytes, round and elongating spermatids. We named this gene as SRG-L (Spermatogenesis Related Gene expressed in late stages of spermatogenic cells, GenBank Accession No. AY352586). The tissue-specific analysis showed a higher expression level in testis and spleen. The gene is mapped on chromosome 8q33.1 and contains 18 exons. The full-length of cDNA is 2,843 bp with an open reading frame (ORF) of 2,625 bp that encodes a 104 kDa protein (874 amino acids) with a putative transmembrane region. The bioinformatics analysis revealed that the SRG-L has two conserved regions, transglutaminase-like homologues domain and D -serine dehydratase domain, rich phosphorylation sites and methylation sites. The SRG-L protein was detected in diplotene/pachytene spermatocytes and spermatids by immunohistochemical staining and Western blot. The results suggest that SRG-L may play definite roles regulating differentiation of germ cells during spermatogenesis, particularly during meiosis and spermiogenesis. Mol. Reprod. Dev. 1075,1083, 2006. © 2006 Wiley-Liss, Inc. [source] Isolation of a novel mouse gene, mSVS-1/SUSD2, reversing tumorigenic phenotypes of cancer cells in vitroCANCER SCIENCE, Issue 6 2007Tetsuo Sugahara We report isolation of a novel tumor-reversing gene, tentatively named SVS-1, encoding a protein of 820 amino acids with localization on the plasma membrane as a type I transmembrane protein. The gene was found among those downregulated in the activated oncogene-v-K-ras-transformed NIH3T3 cells, Ki3T3, with tumorigenic phenotype. SVS-1 protein harbors several functional domains inherent to adhesion molecules. Histochemical staining of mouse tissues using antibody raised against the protein showed the expression of the protein in restricted regions and cells, for example, strongly positive in apical membranes of epithelial cells in renal tubules and bronchial tubes. The protein inducibly expressed in human fibrosarcoma HT1080 cells and cervical carcinoma HeLa cells was found to be localized primarily on the plasma membrane, as stained with antibodies against FLAG tag in the N -terminus and against the C -terminal peptide of the protein. Expression of the protein in cells induced a variety of biological effects on cancer cells: detachment from the substratum and aggregation of cells and growth inhibition in HeLa cells, but no inhibition in non-tumorigenic mouse NIH3T3 cells. Inhibition of clonogenicity, anchorage-independent growth, migration and invasion through Matrigel was also observed. Taken together these results suggest that the SVS-1 gene is a possible tumor-reversing gene. (Cancer Sci 2007; 98: 900,908) [source] Organization of six functional mouse alcohol dehydrogenase genes on two overlapping bacterial artificial chromosomesFEBS JOURNAL, Issue 1 2002Gabor Szalai Mammalian alcohol dehydrogenases (ADH) form a complex enzyme system based on amino-acid sequence, functional properties, and gene expression pattern. At least four mouse Adh genes are known to encode different enzyme classes that share less than 60% amino-acid sequence identity. Two ADH-containing and overlapping C57BL/6 bacterial artificial chromosome clones, RP23-393J8 and -463H24, were identified in a library screen, physically mapped, and sequenced. The gene order in the complex and two new mouse genes, Adh5a and Adh5b, and a pseudogene, Adh5ps, were obtained from the physical map and sequence. The mouse genes are all in the same transcriptional orientation in the order Adh4 - Adh1 - Adh5a - Adh5b - Adh5ps - Adh2 - Adh3. A phylogenetic tree analysis shows that adjacent genes are most closely related suggesting a series of duplication events resulted in the gene complex. Although mouse and human ADH gene clusters contain at least one gene for ADH classes I,V, the human cluster contains 3 class I genes while the mouse cluster has two class V genes plus a class V pseudogene. [source] A review of current large-scale mouse knockout effortsGENESIS: THE JOURNAL OF GENETICS AND DEVELOPMENT, Issue 2 2010Chunmei Guan Abstract After the successful completion of the human genome project (HGP), biological research in the postgenome era urgently needs an efficient approach for functional analysis of genes. Utilization of knockout mouse models has been powerful for elucidating the function of genes as well as finding new therapeutic interventions for human diseases. Gene trapping and gene targeting are two independent techniques for making knockout mice from embryonic stem (ES) cells. Gene trapping is high-throughput, random, and sequence-tagged while gene targeting enables the knockout of specific genes. It has been about 20 years since the first gene targeting and gene trapping mice were generated. In recent years, new tools have emerged for both gene targeting and gene trapping, and organizations have been formed to knock out genes in the mouse genome using either of the two methods. The knockout mouse project (KOMP) and the international gene trap consortium (IGTC) were initiated to create convenient resources for scientific research worldwide and knock out all the mouse genes. Organizers of KOMP regard it as important as the HGP. Gene targeting methods have changed from conventional gene targeting to high-throughput conditional gene targeting. The combined advantages of trapping and targeting elements are improving the gene trapping spectrum and gene targeting efficiency. As a newly-developed insertional mutation system, transposons have some advantages over retrovirus in trapping genes. Emergence of the international knockout mouse consortium (IKMP) is the beginning of a global collaboration to systematically knock out all the genes in the mouse genome for functional genomic research. genesis 48:73,85, 2010. © 2010 Wiley-Liss, Inc. [source] High-affinity triplex-forming oligonucleotide target sequences in mammalian genomesMOLECULAR CARCINOGENESIS, Issue 1 2007Qi Wu Abstract Site-specific recognition of duplex DNA by triplex-forming oligonucleotides (TFOs) provides a promising approach to manipulate mammalian genomes. A prerequisite for successful gene targeting using this approach is that the targeted gene must contain specific, high-affinity TFO target sequences (TTS). To date, TTS have been identified and characterized in only ,37 human or rodent genes, limiting the application of triplex-directed gene targeting. We searched the complete human and mouse genomes using an algorithm designed to identify high-affinity TTS. The resulting data set contains 1.9 million potential TTS for each species. We found that 97.8% of known human and 95.2% of known mouse genes have at least one potential high-affinity TTS in the promoter and/or transcribed gene regions. Importantly, 86.5% of known human and 83% of the known mouse genes have at least one TTS that is unique to that gene. Thus, it is possible to target the majority of human and mouse genes with specific TFOs. We found substantially more potential TTS in the promoter sequences than in the transcribed gene sequences or intergenic sequences in both genomes. We selected 12 mouse genes and 2 human genes critical for cell signaling, proliferation, and/or carcinogenesis, identified potential TTS in each, and determined TFO binding affinities to these sites in vitro. We identified at least one high-affinity, specific TFO binding site within each of these genes. Using this information, many genes involved in mammalian cell proliferation and carcinogenesis can now be targeted. © 2006 Wiley-Liss, Inc. [source] Genomic repertoire of human mesangial cells: comprehensive analysis of gene expression by cDNA array hybridizationNEPHROLOGY, Issue 4 2000Naohiro Yano SUMMARY: Knowing when and where a gene is expressed in a cell often provides a strong clue as to its physiological role. It is estimated the human genome contains 80 000,100 000 genes. Assessment of gene activity on a global genome-wide scale is a fundamental and newly developed experimental strategy to expand the scope of biological investigation from a single gene to studying all genes at once in a systematic way. Capitalizing on the recently developed methodology of cDNA array hybridization, we monitored the simultaneous expression of thousands of genes in primary human mesangial cells. Complex ,- 33P-labelled cDNA probes were prepared from cultured mesangial cells. The probe was hybridized to a high-density array of 18 326 paired target genes. The radioactive hybridization signals were analysed by phosphorimager. Bioinformatics from public genomic databases was utilized to assign a chromosomal location of each expressed transcript. Approximately 7460 different gene transcripts were detected in mesangial cells. Close to 13% (957 genes) were full-length mRNA human transcripts (HTs), the remainder 6503 being expressed sequence tags (ESTs). Using special imaging computer software, the transcriptional level of the 957 HTs was compared with the expression of the ribosomal protein S28 (housekeeping gene). The HTs were also classified by function of the gene product and listed with information on their chromosomal loci. To allow comparison between clinical and experimental studies of gene expression, the detected human gene transcripts were cross-referenced to orthologous mouse genes. Thus, the presented data constitute a quantitative preliminary blueprint of the transcriptional map of the human mesangial cell. The information may serve as a resource for speeding up the discovery of genes underlying human glomerular diseases. The complete listing of the full-length expressed genes is available upon request via E-mail: (Abdalla_Rifai@Brown.edu). [source] Abnormal Vesicular Trafficking in Mouse Models of Hermansky,Pudlak SyndromePIGMENT CELL & MELANOMA RESEARCH, Issue 2000RICHARD T. SWANK Hermansky,Pudlak Syndrome (HPS) is a group of related multigenic recessively inherited disorders which causes abnormalities in the biosynthesis and/or function of three related organelles; melanosomes, platelet-dense granules and lysosomes. These lead, in turn, to hypopigmentation, prolonged bleeding and ceroid deposition. Positional cloning strategies have identified five mouse HPS genes. Two orthologous human diseases (HPS1 and HPS2) have likewise been identified. At least four of the five mouse genes encode proteins involved in the regulation of intracellular vesicle trafficking. The pearl (HPS2) and mocha genes encode the beta3A and delta subunits, respectively, of the AP-3 adaptor complex, which captures organelle membrane proteins at the trans-Golgi apparatus. The protein products of the pallid and gunmetal genes are also important components of the vesicular trafficking machinery. The former interacts with a t-SNARE, syntaxin13, and the latter is the alpha subunit of Rab geranylgeranyltransferase, which renders Rab proteins sufficiently lipophilic to function at their target membranes. The pale ear (HPS1) gene encodes a ubiquitously expressed protein of unknown function. Recent physiological studies have shown that mouse HPS mutants, like their human HPS counterparts, have variably reduced lifespans and may have lung abnormalities. [source] CtBP family proteins: More than transcriptional corepressorsBIOESSAYS, Issue 1 2003G. Chinnadurai CtBP family proteins predominantly function as transcriptional corepressors. Studies with mutant mouse suggest that the two mouse genes, Ctbp1 and Ctbp2, play unique and redundant gene regulatory roles during development.1Ctbp1 -deficient mice are viable, but are small and die early, while Ctbp2 deficiency leads to embryonic lethality. Ctbp2 -null mutation causes defects in axial patterning, heart morphogenesis and neural development. The Ctbp2 mutant phenotype is more severe in the absence of Ctbp1. The studies with Ctbp2 mutant embryos suggest that CtBP can also activate transcription. A plant CtBP homolog, Angustifolia (AN), has recently been identified.2,3AN controls polar elongation of leaf cells via the microtubule cytoskeleton. Microarray analysis suggests that AN also functions as a transcriptional repressor. Thus, the CtBP family proteins control cellular processes by serving as transcriptional activators and regulators of the cytoskeleton as well as transcriptional corepressors. BioEssays 25:9,12, 2003. © 2002 Wiley Periodicals, Inc. [source] | |||||||||||||