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At least 613 records · Page 34Linked to original sources
PubMed2003

Purification and characterization of mouse mast cell proteinase-2 and the differential expression and release of mouse mast cell proteinase-1 and -2 in vivo.

BACKGROUND: Gastrointestinal nematode infection is associated with mucosal mast cell (MMC) hyperplasia. In the mouse, this is accompanied by the release of substantial quantities of the chymase mouse mast cell proteinase-1 (mMCP-1) into the gut lumen and peripheral bloodstream. Expression of mMCP-1 is largely restricted to intraepithelial MMC and is thought to play a role in the regulation of epithelial permeability. MMCs also express mouse mast cell proteinase-2 (mMCP-2), but less is known about the expression or biological function of this proteinase. OBJECTIVES: (1) To purify and characterize mMCP-2. (2) To compare the expression and release of mMCP-2 and mMCP-1 in vivo using specific antibodies. METHODS: Bone marrow-derived mast cells (mBMMCs) were generated from mMCP-1(-/-) BALB/c mice. mMCP-2 was purified, characterized and used to generate rat and sheep polyclonal antibodies. The expression and systemic release of mMCP-1 and -2 were compared in vivo by immunohistochemistry and ELISA. RESULTS: mMCP-2 was successfully purified from mMCP-1(-/-) mBMMC and its identity confirmed by N-terminal amino acid sequencing. mMCP-2 bound [3H]-labelled DFP, indicating the presence of an active serine proteinase catalytic site, but showed little evidence of chymotryptic activity. MMC expressed comparable levels of mMCP-1 and -2 in the jejunum but not in the gastric mucosa, where mMCP-2 was more abundant. Expression of both proteinases increased substantially during primary Nippostrongylus brasiliensis infection and this was accompanied by a substantial increase in peripheral blood levels of mMCP-1 (70 microg/mL on day 12). By contrast, mMCP-2 was not detected in the serum of uninfected mice and only increased to approximately 25 ng/mL on day 12. CONCLUSION: As in the case of mMCP-1, mMCP-2 expression is restricted to MMC. However, mMCP-2 lacks chymase activity, is expressed at higher levels in gastric MMC and appears to be differentially released into the peripheral bloodstream.

Animals↗
PubMed1997

Characterization of the mouse prostaglandin F receptor gene: a transgenic mouse study of a regulatory region that controls its expression in the stomach and kidney but not in the ovary.

BACKGROUND: The actions of prostaglandin F2alpha are mediated by a cell-surface receptor (FP), but little is known about the regulation of FP gene expression. To clarify the mechanisms underlying tissue specific transcription of the mouse FP gene, we isolated and characterized mouse genomic DNA clones encoding FP. RESULTS: Structural analysis revealed that the mouse FP gene is composed of three exons and two introns, and spans more than 11 kilobases. By primer extension and PCR analyses, the major transcription start site was identified as a cytosine nucleotide, but additional sites of transcription initiation were found in the ovary. There was no apparent difference in the FP gene transcription initiation site between the ovary, kidney and stomach. Sequence analysis of the putative promoter region showed only two potential SP-1 binding sites, but no other typical well-known consensus sequences. We generated transgenic mice with the potential promoter region of the FP gene connected to the lacZ reporter gene. Northern blot analysis showed that the pattern of expression of the transgene corresponded to that of FP expression, except in the ovary. Upon analysis by in situ hybridization, the lacZ gene transcripts were found to be expressed in the fundic glands in the stomach, and the cortical tubules in the kidney, in which endogenous FP transcripts were also expressed. On the contrary, expression of lacZ transcripts was not detected in the corpora lutea, where the highest expression of FP mRNA was observed. CONCLUSIONS: These studies suggest that a separate control mechanism exists for FP expression in the ovary, distinct from the expression in the stomach and kidney.

Amino Acid Sequence↗
PubMed2000

Mouse Peg9/Dlk1 and human PEG9/DLK1 are paternally expressed imprinted genes closely located to the maternally expressed imprinted genes: mouse Meg3/Gtl2 and human MEG3.

BACKGROUND: Genomic imprinting significantly influences development, growth and behaviour in mammals. Systematic screening of imprinted genes has been extensively carried out to identify the genes responsible for imprinted phenotypes and to elucidate the biological significance of this phenomenon. In this study, we applied DNA chip technology for isolating paternally expressed imprinted genes (Pegs). We compared the resulting expression profiles of parthenogenetic and fertilized control embryos to identify novel imprinted genes. RESULTS: A novel paternally expressed mouse imprinted gene, Peg9/Dlk1, was identified. Consistent with this finding, the paternal expression of its human homologue, PEG9/DLK1, was also confirmed. These two genes form imprinted gene clusters with the reciprocally imprinted mouse Meg3/Gtl2 and human MEG3 genes that we first identified on distal chromosome 12 and chromosome 14q32, respectively. CONCLUSIONS: As DNA chip technology allows us to quickly screen a large number of genes, using this technology to search for imprinted genes could accelerate the identification of genes responsible for human and mouse genetic diseases. Dlk1 and DLK1, which encode transmembrane proteins, have six EGF-like repeats and show homology to the Delta gene in Drosophila melanogaster. Because of its homology to mammalian Delta homologues, PEG9/DLK1 may contribute to the scoliosis phenotype observed in maternal uniparental disomy 14 (mUPD14) patients.

Animals↗
PubMed2004

The mouse kinome: discovery and comparative genomics of all mouse protein kinases.

We have determined the full protein kinase (PK) complement (kinome) of mouse. This set of 540 genes includes many novel kinases and corrections or extensions to >150 published sequences. The mouse has orthologs for 510 of the 518 human PKs. Nonorthologous kinases arise only by retrotransposition and gene decay. Orthologous kinase pairs vary in sequence conservation along their length, creating a map of functionally important regions for every kinase pair. Many species-specific sequence inserts exist and are frequently alternatively spliced, allowing for the creation of evolutionary lineage-specific functions. Ninety-seven kinase pseudogenes were found, all distinct from the 107 human kinase pseudogenes. Chromosomal mapping links 163 kinases to mutant phenotypes and unlocks the use of mouse genetics to determine functions of orthologous human kinases.

Animals↗
PubMed1969

Mouse leukemia virus: "spontaneous" release by mouse embryo cells after long-term in vitro cultivation.

BALB/c mouse embryo cells maintained in tissue culture on a schedule of rapid transfer at high cell density develop into tumorigenic lines that have lost contact inhibition of cell division. After several months in culture, certain of these lines begin to release mouse leukemia virus. This virus has properties indistinguishable from those of virus found in adult BALB/c mice. The evidence presented here demonstrates that the murine leukemia virus genome must be present in the original embryo cultures. The possibility that the genetic information for making murine leukemia virus is present in a repressed form in every mouse embryo cell is discussed.

Animals↗
PubMed1971

DNA and gene therapy: transfer of mouse DNA to human and mouse embryonic cells by polyoma pseudovirions.

It was demonstrated previously that polyoma pseudovirions (DNA fragments encapsidated by polyoma virus coats) are adsorbed to and uncoated by mouse-embryo cells. 24 hr after infection of secondary mouse-embryo cells with [(3)H]thymidine-labeled pseudovirus, 24% of the total radioactivity found in cells occurred in the nuclear fraction. This nuclear radioactivity represents pseudovirus DNA, as shown by its hybridization with mouse-embryo DNA. Since much of the radioactive material found in the nuclear fraction is sensitive to pancreatic DNase, it is available as uncoated DNA.24 hr after infection of human embryo cells with [(3)H]thymidine-labeled pseudovirions, 7% of the total cellular radioactivity is found in the nuclear fraction of the cells. That this radioactivity represents uncoated pseudoviral DNA was shown by sedimentation of the disrupted nuclear fraction through a neutral sucrose gradient. The pseudoviral DNA in the nuclear fraction has been nicked to some extent, as shown by the heterogeneity of the peaks found after sedimentation of the disrupted nuclear fraction through alkaline sucrose. The experiments demonstrate that polyoma pseudovirions deliver DNA to human cells.

Animals↗
PubMed1993

Transforming growth factor beta 1 (TGF-beta 1) controls expression of major histocompatibility genes in the postnatal mouse: aberrant histocompatibility antigen expression in the pathogenesis of the TGF-beta 1 null mouse phenotype.

The phenotype of the transforming growth factor beta 1 (TGF-beta 1) null mouse has been previously described and is characterized by inflammatory infiltrates in multiple organs leading to a wasting syndrome and death as early as 3 weeks after birth. Since this phenotype occurs in the absence of any detectable pathogen, potential autoimmune disease mechanisms were investigated. We examined major histocompatibility complex (MHC) mRNA expression in tissues of the TGF-beta 1 null mouse and found levels of both the class I and class II MHC mRNA elevated compared to normal or TGF-beta 1 heterozygous littermates. This elevated expression was seen prior to any evidence of inflammatory infiltrates, suggesting a causal relationship between increased MHC expression and activation of immune cell populations. Cell surface expression of MHC molecules was detected by immunohistochemistry and correlated well with mRNA levels. Expression of mRNA for interferon gamma and its receptor was unchanged at the ages when increased MHC expression became apparent. Down-regulation of class I MHC expression by TGF-beta 1 was also demonstrated in vitro in fibroblasts isolated from TGF-beta 1 null mice. These findings suggest that one natural function of TGF-beta 1 is to control expression of both MHC classes. Altered regulation of MHC expression may be a critical step leading to the multifocal inflammation and wasting syndrome seen in the TGF-beta 1 null mouse. These results suggest potential applications for TGF-beta in the management of autoimmune disease, allograft rejection, and other problems associated with altered MHC expression.

Animals↗
PubMed1993

Interleukin 6 inhibits mouse placental lactogen II but not mouse placental lactogen I secretion in vitro.

The mouse placenta produces several polypeptides belonging to the prolactin-growth hormone gene family, including mouse placental lactogen (mPL) I and mPL-II. The present study was undertaken to determine whether the secretion of mPL-I and mPL-II is regulated by interleukin 6 (IL-6), which is present in the placenta and has previously been reported to stimulate the secretion of pituitary members of this gene family. Effects of human and mouse IL-6 on mPL-I and mPL-II secretion were examined in primary cultures of placental cells from days 7, 9, and 12 of pregnancy. IL-6 caused a dose-dependent reduction in the mPL-II concentration in the medium of cells from days 9 and 12 of pregnancy but did not affect the mPL-II concentration in the medium of cells from day 7 of pregnancy or the mPL-I concentration in the medium of cells from days 7 or 9 of pregnancy. The lowest concentration of human IL-6 that significantly inhibited mPL-II secretion was 250 pM. The effect of IL-6 on the mPL-II concentration in the medium was due primarily to inhibition of mPL-II synthesis, which resulted at least partly from a decrease in the steady-state level of mPL-II mRNA. These data raise the possibility that IL-6 may regulate mPL-II production after midpregnancy in vivo.

Animals↗
PubMed1995

Efficient high-resolution genetic mapping of mouse interspersed repetitive sequence PCR products, toward integrated genetic and physical mapping of the mouse genome.

The ability to carry out high-resolution genetic mapping at high throughput in the mouse is a critical rate-limiting step in the generation of genetically anchored contigs in physical mapping projects and the mapping of genetic loci for complex traits. To address this need, we have developed an efficient, high-resolution, large-scale genome mapping system. This system is based on the identification of polymorphic DNA sites between mouse strains by using interspersed repetitive sequence (IRS) PCR. Individual cloned IRS PCR products are hybridized to a DNA array of IRS PCR products derived from the DNA of individual mice segregating DNA sequences from the two parent strains. Since gel electrophoresis is not required, large numbers of samples can be genotyped in parallel. By using this approach, we have mapped > 450 polymorphic probes with filters containing the DNA of up to 517 backcross mice, potentially allowing resolution of 0.14 centimorgan. This approach also carries the potential for a high degree of efficiency in the integration of physical and genetic maps, since pooled DNAs representing libraries of yeast artificial chromosomes or other physical representations of the mouse genome can be addressed by hybridization of filter representations of the IRS PCR products of such libraries.

Animals↗
PubMed1995

Mouse model of human beta zero thalassemia: targeted deletion of the mouse beta maj- and beta min-globin genes in embryonic stem cells.

beta zero-Thalassemia is an inherited disorder characterized by the absence of beta-globin polypeptides derived from the affected allele. The molecular basis for this deficiency is a mutation of the adult beta-globin structural gene or cis regulatory elements that control beta-globin gene expression. A mouse model of this disease would enable the testing of therapeutic regimens designed to correct the defect. Here we report a 16-kb deletion that includes both adult beta-like globin genes, beta maj and beta min, in mouse embryonic stem cells. Heterozygous animals derived from the targeted cells are severely anemic with dramatically reduced hemoglobin levels, abnormal red cell morphology, splenomegaly, and markedly increased reticulocyte counts. Homozygous animals die in utero; however, heterozygous mice are fertile and transmit the deleted allele to progeny. The anemic phenotype is completely rescued in progeny derived from mating beta zero-thalassemic animals with transgenic mice expressing high levels of human hemoglobin A. The beta zero-thalassemic mice can be used to test genetic therapies for beta zero-thalassemia and can be bred with transgenic mice expressing high levels of human hemoglobin HbS to produce an improved mouse model of sickle cell disease.

Animals↗
PubMed1996

Histidine decarboxylase expression in mouse mast cell line P815 is induced by mouse peritoneal cavity incubation.

Phenotype of P815 mouse mast cells changes markedly during culture in the peritoneal cavity of syngenic BDF1 mice. The cells, cultured for 1 week in the peritoneal cavity of syngenic BDF1 mice, proliferate and express high levels of L-histidine decarboxylase (HDC) and mouse mast cell protease (MMCP)-6 mRNAs, indicating the ability of P815 cells to differentiate toward mature connective tissue mast cells. Peritoneal fluid aspirated from P815-inoculated BDF1 mouse and added to cultured P815 cells in vitro was also found to induce HDC mRNA expression, suggesting that at least some of the humoral factors in the peritoneal fluid induce HDC mRNA transcription. Among the erythroid transcription factors, P815 cells expressed GATA-2 but not GATA-1 mRNA before and after the intraperitoneal incubation. In contrast, the expression of NF-E2 subunit p45 disappeared, while expression of subunit mafK was markedly reduced after incubation. Cotransfection assays using HDC-luciferase reporter and p45 and/or mafK expression constructs showed that NF-E2 affects the transactivation of HDC gene. These results suggest that NF-E2 is also an important transcription factor in mast cell differentiation.

Animals↗
PubMed2002

Transcriptional regulation of mouse delta-opioid receptor gene. Ikaros-2 and upstream stimulatory factor synergize in trans-activating mouse delta-opioid receptor gene in T cells.

Considerable evidence indicates that transcription of the delta-opioid receptor (dor) gene is correlated with both the expression of DOR on T cells and the capacity of DOR agonists to modulate the immunological functions of the T cell. We previously reported that increased Ikaros (Ik) binding activity over an Ik-binding site at -378 to -374 (with the translation start site designated as +1) in the mouse dor promoter was required for the enhanced transcription of dor gene in phytohemagglutinin-activated EL-4 cells, a mouse T cell line that constitutively expresses DOR. In the present study, we have analyzed further the mouse dor promoter in EL-4 cells and have demonstrated that Ik-2 homodimers bind to the -378/-374 Ik-binding site and exerts a position-dependent trans-activation effect on the dor promoter. Moreover, an E box (-185 to -180) that binds upstream stimulatory factor is essential for the dor promoter activity in both resting and phytohemagglutinin-activated T cells. Furthermore, we have demonstrated that Ik-2 and upstream stimulatory factor synergize in trans-activating the dor promoter via the putative Ik-binding site and the E box, respectively.

Animals↗
PubMed2003

Regulation and biochemistry of mouse molybdo-flavoenzymes. The DBA/2 mouse is selectively deficient in the expression of aldehyde oxidase homologues 1 and 2 and represents a unique source for the purification and characterization of aldehyde oxidase.

Mouse molybdo-flavoenzymes consist of xanthine oxidoreductase, aldehyde oxidase (AOX1), and two recently identified proteins, AOH1 and AOH2 (aldehyde oxidase homologues 1 and 2). Here we demonstrate that CD-1, C57BL/6, 129/Sv, and other mouse strains synthesize high levels of AOH1 in the liver and AOH2 in the skin. By contrast, the DBA/2 and CBA strains are unique, having a selective deficit in the expression of the AOH1 and AOH2 genes. DBA/2 animals synthesize trace amounts of a catalytically active AOH1 protein. However, relative to CD-1 animals, an over 2 log reduction in the steady-state levels of liver AOH1 mRNA, protein, and enzymatic activity is observed in basal conditions and following administration of testosterone. The DBA/2 mouse represents a unique opportunity to purify AOX1 and compare its enzymatic characteristics to those of the AOH1 protein. The spectroscopy and biochemistry of AOX1 are very similar to those of AOH1 except for a differential sensitivity to the non-competitive inhibitory effect of norharmane. AOX1 and AOH1 oxidize an overlapping set of aldehydes and heterocycles. For most compounds, the substrate efficiency (V(max)/K(m)) of AOX1 is superior to that of AOH1. Alkylic alcohols and acetaldehyde, the toxic metabolite of ethanol, are poor substrates of both enzymes. Consistent with this, the levels of acetaldehyde in the livers of ethanol administered CD-1 and DBA/2 mice are similar, indicating that neither enzyme is involved in the in vivo biotransformation of acetaldehyde.

Aldehyde Oxidoreductases↗
PubMed2006

For dioxin-induced birth defects, mouse or human CYP1A2 in maternal liver protects whereas mouse CYP1A1 and CYP1B1 are inconsequential.

Dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin) induces cleft palate and hydronephrosis in mice, when exposed in utero; these effects are mediated by the aryl hydrocarbon receptor. The Cyp1a1, Cyp1a2, and Cyp1b1 genes are up-regulated by the aryl hydrocarbon receptor. To elucidate their roles in dioxin-induced teratogenesis, we compared Cyp1a1(-/-), Cyp1a2(-/-), and Cyp1b1(-/-) knock-out mice with Cyp1(+/+) wild-type mice. Dioxin was administered (25 microg/kg, gavage) on gestational day 10, and embryos were examined on gestational day 18. The incidence of cleft palate and hydronephrosis was not significantly different in fetuses from Cyp1a1(-/-), Cyp1b1(-/-), and Cyp1(+/+) wild-type mice. To fetuses carried by Cyp1a2(-/-) dams, however, this dose of dioxin was lethal; this effect was absolutely dependent on the maternal Cyp1a2 genotype and independent of the embryonic Cyp1a2 genotype. Dioxin levels were highest in adipose tissue, mammary gland, and circulating blood of Cyp1a2(-/-) mothers, compared with that in the Cyp1(+/+) mothers, who showed highest dioxin levels in liver. More dioxin reached the embryos from Cyp1a2(-/-) dams, compared with that from Cyp1(+/+) dams. Fetuses from Cyp1a2(-/-) dams exhibited a approximately 6-fold increased sensitivity to cleft palate, hydronephrosis, and lethality. Using the humanized hCYP1A1_1A2 transgenic mouse (expressing the human CYP1A1 and CYP1A2 genes in the absence of mouse Cyp1a2 gene), the teratogenic effects of dioxin reverted to the wild-type phenotype. These data indicate that maternal mouse hepatic CYP1A2, by sequestering dioxin and thus altering the pharmacokinetics, protects the embryos from toxicity and birth defects; substitution of the human CYP1A2 trans-gene provides the same protection. In contrast, neither CYP1A1 nor CYP1B1 appears to play a role in dioxin-mediated teratogenesis.

Abnormalities, Drug-Induced↗
PubMed2005

The Mouse Tumor Biology Database: integrated access to mouse cancer biology data.

Mice have long been used as models for the study of human cancer. The National Cancer Institute has included among its research areas of extraordinary opportunity the development of new mouse genetic models of human cancer and the exploration of cancer imaging as a research tool. Because of the volume and interconnectedness of relevant data, the creation and maintenance of bioinformatics resources of mouse tumor biology is necessary to facilitate current and future cancer research. The Mouse Tumor Biology (MTB) Database provides electronic access to data generated through the study of spontaneous and induced tumors in genetically defined mice (inbred, hybrid, spontaneous and induced mutant, and genetically engineered strains of mice).

Animals↗
PubMed2005

Relationship between radiobiological hypoxia in a C3H mouse mammary carcinoma and osteopontin levels in mouse serum.

PURPOSE: To investigate the possible relationship between radiobiological hypoxia in a C3H mouse mammary carcinoma and osteopontin (OPN) levels measured in mouse serum. MATERIAL AND METHODS: Experiments were performed in CDF1 mice that were either non-tumour bearing or with different sized tumours implanted in the right rear foot. Osteopontin levels in extracted mouse blood serum and tissue from the transplanted tumours were measured using an ELISA assay. The tumour oxygenation status was estimated using the Eppendorf Histograph and the fraction of oxygen partial pressure (pO2) values =5 mm Hg (HF5) was calculated. Necrosis was measured in haematoxylin and eosin-stained sections. Tumour hypoxia was increased by placing animals in a low-oxygen (10%) environment. Single radiation doses (240 kV x-rays) were given locally to tumours under ambient or clamped conditions and response assessed using a tumour control assay. RESULTS: Serum OPN levels increased linearly with increasing tumour volume and this increase correlated with tumour OPN. HF5 and necrosis also increased with increasing tumour volume, but this increase was non-linear. Converting the HF5 results into equivalent tumour volume gave results that were directly correlated to OPN serum levels. Placing mice in a 10% oxygen environment for 12 hours significantly increased HF5. However, serum OPN only increased if reoxygenation occurred before measurement. Radiobiological hypoxic fraction in this tumour model did not change with increasing tumour size, but the total number of hypoxic cells did increase. CONCLUSIONS: These findings suggest that serum OPN measurement may predict the proportion of hypoxic cells in this tumour model, although increased serum OPN levels simply resulting from an increased tumour burden can not be ruled out.

Animals↗
PubMed1991

A pilot study comparing mouse and mouse-emulating interface devices for graphic input.

Adaptive interface devices make it possible for individuals with physical disabilities to use microcomputers and thus perform many tasks that they would otherwise be unable to accomplish. Special equipment is available that purports to allow functional access to the computer for users with disabilities. As technology moves from purely keyboard applications to include graphic input, it will be necessary for assistive interface devices to support graphics as well as text entry. Headpointing systems that emulate the mouse in combination with on-screen keyboards are of particular interest to persons with severe physical impairment such as high level quadriplegia. Two such systems currently on the market are the HeadMaster and the Free Wheel. The authors have conducted a pilot study comparing graphic input speed using the mouse and two headpointing interface systems on the Macintosh computer. The study used a single subject design with six able-bodied subjects, to establish a baseline for comparison with persons with severe disabilities. Results of these preliminary data indicated that the HeadMaster was nearly as effective as the mouse and that it was superior to the Free Wheel for graphics input. This pilot study, however, demonstrated several experimental design problems that need to be addressed to make the study more robust. It also demonstrated the need to include the evaluation of text input so that the effectiveness of the interface devices with text and graphic input could be compared.

Adult↗
PubMed2005

The SOD1 transgene in the G93A mouse model of amyotrophic lateral sclerosis lies on distal mouse chromosome 12.

The SOD1G93A transgenic mouse strain which carries a human mutant Cu/Zn superoxide dismutase transgene array is a widely studied model of amyotrophic lateral sclerosis. These mice have been used in many breeding experiments to look for interactions with other loci, including transgenic and gene targeted mutations. Therefore, we decided to map the site of the transgene insertion as this may affect the outcome of such breeding experiments. In a fluorescence in situ hybridization experiment we determined that the SOD1G93A transgene insertion site lies on distal mouse chromosome 12. This chromosome also carries the 'Legs at odd angles' locus, which is an entirely unrelated mutation in the dynein heavy chain gene that we have been studying. We have analysed data from a SOD1G93AxLoa cross and determined that the site of the transgene insertion lies proximal of the dynein heavy chain gene on mouse chromosome 12.

Amyotrophic Lateral Sclerosis↗