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‣ Experimentos de microarrays e teoria da resposta ao item; Microarryas experiments and Iten Response Theory

Neves, Carlos Eduardo
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Dissertação de Mestrado Formato: application/pdf
Publicado em 25/02/2010 Português
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Recentemente desenvolvida, a biotecnologia denominada por Microarrays permite o monitoramento simultâneo dos valores de expressão gênica de centenas de milhares de genes, fator este que traz uma nova interpretação aos resultados obtidos em pesquisas desenvolvidas nas mais diversas áreas do conhecimento incluindo, por exemplo, a Farmacologia e Medicina, uma vez que os resultados obtidos são interpretados ao nível molecular. Contudo, apesar de muita tecnologia ser empregada à técnica de Microarrays, sua aplicação ainda ocasiona algumas complicações decorrentes, por exemplo, das inúmeras fontes de variação existentes, da escala das respostas ou da natural dificuldade de se analisar uma grande quantidade de fragmentos genéticos avaliados sob poucas unidades experimentais. Frente a estas complicações, atualmente, muitas são as propostas metodológicas de análises estatísticas para atenuar ou eliminar os problemas inerentes à técnica de Microarrays e propiciar a extração de resultados mais confiáveis a partir dos valores de expressão gênica, porém muitos desafios ainda persistem. Sob esta colocação, o presente trabalho procurou explorar duas metodologias de análise estatística alternativas no que diz respeito a seus conceitos...

‣ Visceral leishmaniasis in congenic mice of susceptible and resistant phenotypes: immunosuppression by adherent spleen cells.

Nickol, A D; Bonventre, P F
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /10/1985 Português
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Visceral leishmaniasis is one of several parasitic diseases of humans characterized by immune suppression. A murine model of disseminated leishmaniasis utilizing inbred strains of specific genetic constitution was used to study the mechanisms of immunosuppression elicited during the course of infection. Resistant (Lshr) and susceptible (Lshs) strains of mice were challenged with amastigotes of Leishmania donovani and evaluated as to immune status at intervals between 2 and 40 weeks after challenge. The proliferative responses of splenic lymphocytes to T-cell mitogens, a B-cell mitogen, and parasite antigens were measured to evaluate the relative immune status of parasitized mice and noninfected control mice. Lymphocytes from resistant C3Heb/FeJ (C3H) mice responded normally to concanavalin A and phytohemagglutinin throughout the course of infection. Parasite antigen responses appeared 2 weeks after challenge of C3H mice and remained vigorous for periods up to 6 months. In contrast, immune suppression during infection was profound in both the curing (C57B1/10) and noncuring (B10.D2) phenotypes of Lshs congenic mice. Both Lshs strains developed severe infection as evidenced by high parasite burdens in the liver and spleen 4 to 5 weeks after challenge; splenic lymphocytes taken from these mice between 2 and 8 weeks became increasingly unresponsive to the T-cell mitogens as well as to parasite antigens. The noncuring B10.D2 mice which suffered chronic infection continued to be suppressed for as long as 40 weeks. C57B1/10 (curing) mice...

‣ Delineation of two defects responsible for T-cell hyporesponsiveness to concanavalin A in MRL congenic mice.

Cameron, R; Waterfield, J D
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /10/1986 Português
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MRL-lpr mice and their congenic counterparts MRL-+ spontaneously develop an autoimmune disease that resembles systemic lupus erythematosus in humans. The two strains, although congenic, differ by a considerable number of disease parameters, reflecting the expression of the lpr autosomal recessive gene. One paradox that has developed out of the work utilizing the congenic mice is that the gene responsible for lymphoproliferation also appears to be responsible for the inability of T cells to respond to proliferative signals in vitro. In this paper we investigated a possible lpr gene-encoded macrophage defect in these mice. It was found, however, that both the MRL-+ and MRL-lpr mice failed to divide in response to Con A, the lack of division correlating with an inability to secrete the growth promoter interleukin-2. In MRL-+ mice and young MRL-lpr mice this non-responsiveness was corrected by the addition of normal CBA PEC. The defect could not be explained by a failure of MRL-+ or MRL-lpr peritoneal exudate cells to quantitatively or qualitatively provide a source of interleukin-1 to Con A-activated T cells or by the possibility that the peritoneal exudate cells were blocked in their function by the presence of sera-derived autoantibodies and/or immune complexes on their membranes. We postulate that the inability of T cells to proliferate in MRL congenic mice can be explained by two defects: the failure of antigen-presenting cells in MRL-+ and MRL-lpr to provide the necessary signals to immunocompetent T cells...

‣ Antigen-specific T-cell hyporesponsiveness in MRL congenic mice can be explained by two independent cellular defects.

Waterfield, J D; Fairhurst, M; Chu, R; Levy, J G
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /06/1987 Português
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MRL-+, MRL-lpr and B6-lpr have been shown to be useful models in studying systemic lupus erythematosus. MRL-lpr and B6-lpr differ from their congenic counterparts by the presence and expression of the homozygous recessive lymphoproliferation (lpr) gene. One manifestation of this gene is a massive T-cell proliferation that results in a generalized lymphadenopathy in older animals. A paradox that has developed out of the work utilizing the congenic mice is that the gene responsible for lymphoproliferation also appears to be responsible for the inability of T cells to respond to proliferative signals in vitro. In this paper we investigate the basis for this hyporesponsiveness in antigen-induced activation of proliferation and antibody synthesis. We have demonstrated that spleen cells from both MRL-+ and MRL-lpr mice gave minimal stimulation in a one-way mixed lymphocyte reaction against allogeneic T cells. These findings were extended to include antigen-specific proliferation involving antigen that must be processed and presented to responder lymphocytes in a H-2 restricted manner. Thus, MRL-+ and MRL-lpr spleen cells pulsed with ferredoxin also failed to stimulate ferredoxin-primed T cells from B10.Br animals in vitro. We then investigated whether any T-cell defect(s) was also contributing to this proliferative hyporesponsiveness. T lymphocytes from the spleen of MRL-+...

‣ Immune responses in congenic mice to multiple antigen peptides based on defined epitopes from the malaria antigen Pf332.

Ahlborg, N; Andersson, R; Perlmann, P; Berzins, K
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /08/1996 Português
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Repeat sequences from the Plasmodium falciparum blood stage antigen Pf332 frequently comprise the pentapeptide VTEEI, an epitope recognized by certain parasite neutralizing antibodies. This B-cell epitope was assembled in an octavalent multiple antigen peptide (MAP) system either as trimers (VTEEI)3 (MAP1) or as an integral part of a naturally occurring Pf332 undecamer repeat sequence SVTEEIAEEDK (MAP2). Characteristics of the immunogenicity of these subunit constructs were evaluated in H-2 congenic mice. MAP1 generated antibody responses in mice of the H-2d, H-2k and H-2q haplotypes, but not in H-2b or H-2s mice, whereas MAP2 only induced antibodies in mice of H-2k haplotype. When analysing T-cell responses induced by the MAP, lymph node cells from responder strains primed in vivo with MAP1 proliferated in response to restimulation with both MAP1 and the peptide (VTEEI)3. MAP2, however, did not induce a detectable T-cell proliferation. Additionally, the lack of antibody response to MAP1 in H-2b mice could be circumvented by combining the MAP1 peptide and a H-2b-restricted T-cell epitope in a diepitope MAP construct. Despite the fact that the motif VTEEI has not been identified in Pf332 sequences in the form of a trimer, MAP1 did induce Pf332 protein-reactive antibodies. Assembly of multimers of short defined epitopes in MAP constitutes an interesting approach for the design of polyvalent subunit immunogens.

‣ Molecular Genetic Analysis of Two Loci (Ity2 and Ity3) Involved in the Host Response to Infection With Salmonella Typhimurium Using Congenic Mice and Expression Profiling

Sancho-Shimizu, Vanessa; Khan, Rabia; Mostowy, Serge; Larivière, Line; Wilkinson, Rosalie; Riendeau, Noémie; Behr, Marcel; Malo, Danielle
Fonte: Copyright © 2007 by the Genetics Society of America Publicador: Copyright © 2007 by the Genetics Society of America
Tipo: Artigo de Revista Científica
Publicado em /10/2007 Português
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Numerous genes have been identified to date that contribute to the host response to systemic Salmonella Typhimurium infection in mice. We have previously identified two loci, Ity2 and Ity3, that control survival to Salmonella infection in the wild-derived inbred MOLF/Ei mouse using a (C57BL/6J × MOLF/Ei)F2cross. We validated the existence of these two loci by creating congenic mice carrying each quantitative trait locus (QTL) in isolation. Subcongenic mice generated for each locus allowed us to define the critical intervals underlying Ity2 and Ity3. Furthermore, expression profiling was carried out with the aim of identifying differentially expressed genes within the critical intervals as potential candidate genes. Genomewide expression arrays were used to interrogate expression differences in the Ity2 congenics, leading to the identification of a new candidate gene (Havcr2, hepatitis A virus cellular receptor 2). Interval-specific oligonucleotide arrays were created for Ity3, identifying one potential candidate gene (Chi3l1, chitinase 3-like 1) to be pursued further. The combination of the use of congenics in QTL confirmation and fine mapping and in the identification of candidate genes by expression profiling has been successful and represents a step toward quantitative gene(s) identification.

‣ Allelic variation of the Tas1r3 taste receptor gene selectively affects taste responses to sweeteners: evidence from 129.B6-Tas1r3 congenic mice

Inoue, Masashi; Glendinning, John I.; Theodorides, Maria L.; Harkness, Sarah; Li, Xia; Bosak, Natalia; Beauchamp, Gary K.; Bachmanov, Alexander A.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
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The Tas1r3 gene encodes the T1R3 receptor protein, which is involved in sweet taste transduction. To characterize ligand specificity of the T1R3 receptor and the genetic architecture of sweet taste responsiveness, we analyzed taste responses of 129.B6-Tas1r3 congenic mice to a variety of chemically diverse sweeteners and glucose polymers with three different measures: consumption in 48-h two-bottle preference tests, initial licking responses, and responses of the chorda tympani nerve. The results were generally consistent across the three measures. Allelic variation of the Tas1r3 gene influenced taste responsiveness to nonnutritive sweeteners (saccharin, acesulfame-K, sucralose, SC-45647), sugars (sucrose, maltose, glucose, fructose), sugar alcohols (erythritol, sorbitol), and some amino acids (d-tryptophan, d-phenylalanine, l-proline). Tas1r3 genotype did not affect taste responses to several sweet-tasting amino acids (l-glutamine, l-threonine, l-alanine, glycine), glucose polymers (Polycose, maltooligosaccharide), and nonsweet NaCl, HCl, quinine, monosodium glutamate, and inosine 5′-monophosphate. Thus Tas1r3 polymorphisms affect taste responses to many nutritive and nonnutritive sweeteners (all of which must interact with a taste receptor involving T1R3)...

‣ Genome wide microarray expression analysis of CD4+ T cells from NOD congenic mice identifies Cd55 (Daf1) and Acadl as candidate genes for type 1 diabetes

Irie, Junichiro; Reck, Brian; Wu, Yuehong; Wicker, Linda S.; Howlett, Sarah; Rainbow, Daniel; Feingold, Eleanor; Ridgway, William M.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 15/01/2008 Português
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NOD.Idd3/5 congenic mice have insulin dependent diabetes (Idd) regions on chromosomes one (Idd5) and three (Idd3) respectively derived from the non-diabetic strains B10 and B6. NOD.Idd3/5 mice are almost completely protected from type 1 diabetes (T1D) but the genes within Idd3 and Idd5 responsible for the disease-altering phenotype have been only partially characterized. To test the hypothesis that candidate Idd genes could be identified by differential gene expression between the diabetes-susceptible NOD strain and a protected NOD congenic strain, genome-wide microarray expression analysis using an empirical Bayes method was applied to RNA purified from activated NOD and NOD.Idd3/5 CD4+ T cells. Remarkably, the top ten most differentially expressed genes were all from the Idd5 region on chromosome one, validating our central hypothesis. The two genes with the greatest differential RNA expression were those encoding decay-accelerating factor (DAF, also known as CD55) and acetyl-Coenzyme A dehydrogenase, long-chain (ACADL), which are located in the Idd5.4 and Idd5.3 regions, respectively. Neither gene has been implicated previously in the pathogenesis of T1D. In the case of DAF, differential expression of mRNA was extended to the protein level; NOD CD4+ T cells expressed higher levels of cell-surface DAF compared with NOD.Idd3/5 CD4+ T cells following activation with anti-CD3 and anti-CD28. DAF upregulation was shown to be IL-4 dependent and blocked under Th1 conditions. These results validate the approach of using congenic mice together with genome-wide analysis of tissue-specific gene expression to identify novel candidate genes in T1D.

‣ Strial microvascular pathology and age-associated endocochlear potential decline in NOD congenic mice

Ohlemiller, Kevin K.; Rice, Mary E. Rybak; Gagnon, Patricia M.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
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NOD/ShiLtJ (previously NOD/LtJ) inbred mice show polygenic autoimmune disease and are commonly used to model autoimmune-related Type I diabetes, as well as Sjogren’s syndrome. They also show rapidly progressing hearing loss, partly due to the combined effects of Cdh23ahl and Ahl2. Congenic NOD.NON-H2nb1/LtJ mice, which carry corrective alleles within the H2 histocompatibility gene complex, are free from diabetes and other overt signs of autoimmune disease, but still exhibit rapidly progressive hearing loss. Here we show that cochlear pathology in these congenics broadly includes hair cell and neuronal loss, plus endocochlear potential (EP) decline from initially normal values after 2 months of age. The EP reduction follows often dramatic degeneration of capillaries in stria vascularis, with resulting strial degeneration. The cochlear modiolus in the congenic mice also features perivascular inclusions that resemble those in some mouse autoimmune models. We posit that cochlear hair cell/neural and strial pathology in NOD.NON-H2nb1 mice arise independently. While sensory cell loss may be closely tied to Cdh23ahl and Ahl2, the strial microvascular pathology and modiolar anomalies we observe may arise from alleles on the NOD background related to immune function. Age-associated EP decline in NOD.NON-H2nb1 mice may model forms of strial age-related hearing loss caused principally by microvascular disease. The remarkable strial capillary loss in these mice may also be useful for studying the relation between strial vascular insufficiency and strial function.

‣ Clinical Chemistry of Congenic Mice with Quantitative Trait Loci for Predicted Responses to Trypanosoma congolense Infection▿ †

Rathkolb, Birgit; Noyes, Harry A.; Brass, Andy; Dark, Paul; Fuchs, Helmut; Gailus-Durner, Valérie; Gibson, John; de Angelis, Martin Hrabé; Ogugo, Moses; Iraqi, Fuad; Kemp, Steve J.; Naessens, Jan; Pope, Mathew E.; Wolf, Eckhard; Agaba, Morris
Fonte: American Society for Microbiology (ASM) Publicador: American Society for Microbiology (ASM)
Tipo: Artigo de Revista Científica
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Trypanosoma congolense is a protozoan parasite that causes severe diseases in livestock. Three major quantative trait loci (QTL), Tir1, Tir2, and Tir3, control the survival time of mice after infection with T. congolense. Congenic mice carrying the C57BL/6 resistance alleles on the A/J background were developed for each of these loci. The congenic mice were used to physically map the regions containing the QTL gene(s) and to investigate the physiological effect of each locus. Clinical chemistry data for infected A/J, C57BL/6, and BALB/c mice were obtained for 15 analytes at five time points. Congenic mice were assessed for survival, parasitemia, and anemia as well as seven clinical-chemical analytes. The survival times were significantly increased in the Tir1 and Tir2 mice but not Tir3 congenic mice. The survival time of the parental inbred mice correlated negatively with parasitemia but positively with alanine aminotransferase activities in serum, suggesting that inflammatory reactions in the liver had a beneficial effect possibly associated with reduced parasitemia. However, there was no difference in parasitemia or liver enzyme activities of Tir1 and Tir2 congenic mice relative to their controls, showing that survival, parasitemia...

‣ Tryptophan Hydroxylase 2 Genotype Determines Brain Serotonin Synthesis but Not Tissue Content in C57Bl/6 and BALB/c Congenic Mice

Siesser, William B.; Zhang, Xiaodong; Jacobsen, Jacob P.R.; Sotnikova, Tatyana D.; Gainetdinov, Raul R.; Caron, Marc G.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
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Tryptophan hydroxylase 2 (TPH2) catalyzes the rate-limiting step in the synthesis of brain serotonin (5-HT). In a previous report, a single nucleotide polymorphism in mTph2 (C1473G) reduced 5-HT synthesis by 55%. Mouse strains expressing the 1473C allele, such as C57Bl/6, have higher 5-HT synthesis rates than strains expressing the 1473G allele, such as BALB/c. Many studies have attributed strain differences to Tph2 genotype without ruling out the potential role of alterations in other genes. To test the role of the C1473G polymorphism in strain differences, we generated C57Bl/6 and BALB/c mice congenic for the Tph2 locus. We found that the 1473G allele reduced 5-HT synthesis in C57Bl/6 mice but had no effect on 5-HT tissue content except for a slight reduction (15%) in the frontal cortex. In BALB/c mice, the 1473C allele increased 5-HT synthesis but again did not affect 5-HT tissue content. At the same time, 5-hydroxyindoleacetic acid (5-HIAA) was significantly elevated in BALB/c congenic mice. In C57Bl/6 mice, there was no effect of genotype on 5-HIAA levels. BALB/c mice had lower expression of monoamine oxidase A and B than C57Bl/6 mice, but there was no effect of Tph2 genotype. On the tail suspension test, escitalopram treatment reduced immobility regardless of genotype. These data demonstrate that the C1473G polymorphism determines differences in 5-HT synthesis rates among strains but only minimally affects 5-HT tissue levels.

‣ A caveat for T cell transfer studies: generation of cytotoxic anti-Thy1.2 antibodies in Thy1.1 congenic mice given Thy1.2+ tumors or T cells

McKenna, Kyle C.; Miguel, Rodolfo D. Vicetti; Beatty, Kelly M.; Bilonick, Richard A.
Fonte: Society for Leukocyte Biology Publicador: Society for Leukocyte Biology
Tipo: Artigo de Revista Científica
Publicado em /02/2011 Português
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Thy 1.1 congenic mice given Thy 1.2+ tumors or T cells generate cytotoxic anti-Thy 1.2 antibody responses that delete transferred Thy 1.2+ T-cells.

‣ Dissecting Genetic Control of Autoimmunity in NOD Congenic Mice

Ridgway, William M.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em //2006 Português
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My lab investigates genetic control of autoimmune disease and autoimmune phenotypes using a series of nonobese diabetic (NOD) congenic mice. NOD congenic mice have regions from B6/B10 introgressed onto the NOD genetic background, which reduces the severity/incidence of autoimmune diabetes. We have demonstrated, however, that while diabetes is reduced, other autoimmune phenotypes and diseases arise in NOD congenic mice. Mapping the genomic regions responsible for these phenotypes has produced novel insights into genetic control of autoimmunity. This review will illustrate some of the genetically controlled phenotypes we have investigated, which shed light upon autoimmune features relevant to human type 1 diabetes, systemic lupus erythematosus, and primary biliary cirrhosis.

‣ Searching for Genomic Region of High-Fat Diet-Induced Type 2 Diabetes in Mouse Chromosome 2 by Analysis of Congenic Strains

Kobayashi, Misato; Ohno, Tamio; Ihara, Kunio; Murai, Atsushi; Kumazawa, Mayumi; Hoshino, Hiromi; Iwanaga, Koichiro; Iwai, Hiroshi; Hamana, Yoshiki; Ito, Mikako; Ohno, Kinji; Horio, Fumihiko
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em 01/05/2014 Português
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SMXA-5 mice are a high-fat diet-induced type 2 diabetes animal model established from non-diabetic SM/J and A/J mice. By using F2 intercross mice between SMXA-5 and SM/J mice under feeding with a high-fat diet, we previously mapped a major diabetogenic QTL (T2dm2sa) on chromosome 2. We then produced the congenic strain (SM.A-T2dm2sa (R0), 20.8–163.0 Mb) and demonstrated that the A/J allele of T2dm2sa impaired glucose tolerance and increased body weight and body mass index in the congenic strain compared to SM/J mice. We also showed that the combination of T2dm2sa and other diabetogenic loci was needed to develop the high-fat diet-induced type 2 diabetes. In this study, to narrow the potential genomic region containing the gene(s) responsible for T2dm2sa, we constructed R1 and R2 congenic strains. Both R1 (69.6–163.0 Mb) and R2 (20.8–128.2 Mb) congenic mice exhibited increases in body weight and abdominal fat weight and impaired glucose tolerance compared to SM/J mice. The R1 and R2 congenic analyses strongly suggested that the responsible genes existed in the overlapping genomic interval (69.6–128.2 Mb) between R1 and R2. In addition, studies using the newly established R1A congenic strain showed that the narrowed genomic region (69.6–75.4 Mb) affected not only obesity but also glucose tolerance. To search for candidate genes within the R1A genomic region...

‣ Mast cell-derived TNF can exacerbate mortality during severe bacterial infections in C57BL/6-KitW-sh/W-sh mice

Piliponsky, A.; Chen, C.C.; Grimbaldeston, M.; Burns-Guydish, S.; Hardy, J.; Kalesnikoff, J.; Contag, C.; Tsai, M.; Galli, S.
Fonte: Amer Soc Investigative Pathology Inc Publicador: Amer Soc Investigative Pathology Inc
Tipo: Artigo de Revista Científica
Publicado em //2010 Português
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We used mast cell-engrafted genetically mast cell-deficient C57BL/6-Kit(W-sh/W-sh) mice to investigate the roles of mast cells and mast cell-derived tumor necrosis factor in two models of severe bacterial infection. In these mice, we confirmed findings derived from studies of mast cell-deficient WBB6F(1)-Kit(W/W-v) mice indicating that mast cells can promote survival in cecal ligation and puncture (CLP) of moderate severity. However, we found that the beneficial role of mast cells in this setting can occur independently of mast cell-derived tumor necrosis factor. By contrast, using mast cell-engrafted C57BL/6-Kit(W-sh/W-sh) mice, we found that mast cell-derived tumor necrosis factor can increase mortality during severe CLP and can also enhance bacterial growth and hasten death after intraperitoneal inoculation of Salmonella typhimurium. In WBB6F(1)-Kit(W-sh/W-sh) mice, mast cells enhanced survival during moderately severe CLP but did not significantly change the survival observed in severe CLP. Our findings in three types of genetically mast cell-deficient mice thus support the hypothesis that, depending on the circumstances (including mouse strain background, the nature of the mutation resulting in a mast cell deficiency, and type and severity of infection)...

‣ Behavioural analysis of congenic mouse strains confirms stress-responsive loci on chromosomes 1 and 12

Jawahar, M.C.; Brodnicki, T.C.; Quirk, F.; Wilson, Y.M.; Murphy, M.
Fonte: Springer US Publicador: Springer US
Tipo: Artigo de Revista Científica
Publicado em //2008 Português
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The way in which animals respond to stressful environments correlates with anxiety-related behaviour. To begin identifying the genetic factors that influence anxiety, we have studied the stress–responsiveness of inbred mouse strains using a modified form of the open field activity test (OFA), termed the elevated (e) OFA. In particular, two strains show high (DBA/2J) or low (C57BL/6J) stress–responsiveness in the eOFA. Genetic studies of an F2 intercross between these two strains previously identified two regions, on chromosomes (Chr) 1 and 12, linked to anxiety-related behaviour. To confirm that these regions contain loci for stress–responsiveness, we established separate congenic mouse strains for the linked Chr1 and Chr12 regions. Each congenic strain harbours a DBA/2J-derived interval encompassing the linked region on the C57BL/6J genetic background: the congenic intervals are between, but not including ∼48.6 Mb and ∼194.8 Mb on Chr1, and ∼36.2 Mb and the distal end of Chr12. Cohorts of DBA/2J, C57BL/6J and congenic mice were analysed for a series of stress–responsive phenotypes using the eOFA test. Both congenic strains had significantly different stress–responsive phenotypes compared to the low-stress C57BL/6J parental strain...

‣ Innate Resistenz gegen Litomosoides sigmodontis (Nematoda, Filarioidea) in der Labormaus : Untersuchungen zur Genetik, Genomik, Parasitologie und Immunologie Mikrofilarämieresistenz-kongener Labormausstämme; Genetics, genomics, parasitology and immunology of innate resistance to Litomosoides sigmodontis (Nematoda, Filarioidea) microfilariae in mfr (microfilaraemia resistance locus) congenic laboratory mouse strains

Schumacher, Stefan
Fonte: Universidade de Tubinga Publicador: Universidade de Tubinga
Tipo: Dissertação
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Filarien sind in Wirbeltieren parasitierende Nematoden mit in der Regel ausgeprägter Wirtsspezifität, die das Immunsystem ihrer Wirte modulieren und dadurch der Immunabwehr entgehen. Dies gelingt jedoch nur in geeigneten, suszeptiblen Wirten. Genetische Unterschiede zwischen den Individuen einer möglichen Wirtspopulation scheinen dabei eine wichtige Rolle zu spielen. Untersuchungen an der Nagetierfilarie Litomosoides sigmodontis in der Labormaus erlauben die Fokussierung auf die genetischen Determinanten für Resistenz und Suszeptibilität. In DBA/1-Mäusen werden injizierte Mikrofilarien von L. sigmodontis innerhalb der ersten ein bis zwei Tage eliminiert, bei BALB/c-Mäusen zirkulieren sie teilweise länger als einen Monat im Blut. Mäusestämme, die innerhalb von vier Tagen Mikrofilarien vollständig eliminieren, werden hier als resistent, solche mit längerer Mikrofilarämie als suszeptibel definiert. Durch Kreuzung beider Stämme und anschließende serielle Rückkreuzung resistenter Nachkommen mit BALB/c wurde ein zu BALB/c kongener Mäusestamm etabliert (BALB/c.DBA/1-mfr), der einen resistenten Phänotyp zeigt. Aufgrund der Spaltungsverhältnisse bei diesen Kreuzungen kann ein monogener, autosomaler und dominanter Erbgang für diese Resistenz angenommen werden. Mittels genomweiter Mikrosatellitenanalyse konnte der Mikrofilarämie-Resistenzlocus (mfr) auf Chromosom 12 distal des Centromers in einer Region zwischen 56 und 61 cM lokalisiert werde. Daneben scheinen 2 weitere Loci auf den Chromosomen 3 und 9 modulierend auf die Ausprägung der Resistenz zu wirken...

‣ The influence of the NOD Nss1/Idd5 loci on sialadenitis and gene expression in salivary glands of congenic mice

Hjelmervik, Trond Ove R; Lindqvist, Anna-Karin; Petersen, Kjell; Johannesson, Martina; Stavrum, Anne-Kristin; Johansson, Åsa; Jonsson, Roland; Holmdahl, Rikard; Bolstad, Anne Isine
Fonte: BioMed Central Publicador: BioMed Central
Tipo: Artigo de Revista Científica
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The nonobese diabetic (NOD) Nss1 and Idd5 loci have been associated with sialadenitis development in mice. In this study the NOD Nss1 and Idd5 loci were backcrossed onto the healthy control strain B10.Q by using the speed congenic breeding strategy, resulting in three congenic strains: B10.Q.Nss1, B10.Q.Nss1/Idd5 heterozygous and B10.Q.Nss1/Idd5 homozygous. We investigated the effects of the Nss1 and Idd5 loci on sialadenitis and gene expression in NOD congenic mice. One submandibular salivary gland from each mouse was used for histological analysis of sialadenitis, whereas the contralateral salivary gland was used for gene expression profiling with the Applied Biosystems Mouse Genome Survey chip v.1.0. The results were validated using quantitative reverse transcriptase PCR. The NOD Nss1 and Idd5 loci had clear influence on the onset and progression of sialadenitis in congenic mice. Double congenic mice exhibited the most severe phenotype. We successfully identified several genes that are located in the NOD congenic regions to be differentially expressed between the congenic strains and the control strain. Several of these were found to be co-regulated, such as Stat1, complement component C1q genes and Tlr12. Also, a vast contingency of interferon-regulated genes (such as Ltb...

‣ Extracellular Superoxide Dismutase Polymorphism in Mice: Allele- Specific Effects on Phenotype

Jun, Sujung; Pierce, Anson; Dory, Ladislav
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
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Extracellular superoxide dismutase (ecSOD) protects the extracellular matrix (ECM) from oxidative stress. We previously reported a new allele for ecSOD, expressed in 129P3/J mice (129), which differs from the wild-type (wt), expressed in C57BL/6J and other strains, by two amino acid substitutions and a 10 bp deletion in the 3' UTR of the mRNA [1]. The newly discovered allele is associated with a phenotype of significantly increased circulating and heparin-releasable enzyme activities and levels. In order to examine the properties of the two forms of ecSOD in an identical environment we generated, by extensive backcrossing of ecSOD heterozygous progeny to C57BL/6J females, a congenic C57 strain with the 129 (or wt) allele of ecSOD. These mice are homozygous for nearly 5,000 SNPs across all chromosomes, as determined by Affymetrix Parallele Mouse 5K SNP panel. The present study describes the generation of the congenic mice (genetically >99.8 % identical) and their ecSOD phenotype. The congenic mice plasma ecSOD activities before and after heparin administration recapitulate the differences reported in the founder mice. Tissue enzyme distribution is similar in both congenic groups, although the 129 allele is associated with higher levels of enzyme expression despite lower levels of enzyme mRNA. In these characteristics the phenotype is also allele driven...

‣ Major histocompatibility complex-conferred resistance to Theiler's virus-induced demyelinating disease is inherited as a dominant trait in B10 congenic mice.

Patick, A K; Pease, L R; David, C S; Rodriguez, M
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /11/1990 Português
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Intracerebral inoculation of Theiler's murine encephalomyelitis virus into susceptible strains of mice produces chronic demyelinating disease in the central nervous system characterized by persistent viral infection. Immunogenetic data suggest that genes from both major histocompatibility complex (MHC) and non-MHC loci are important in determining susceptibility or resistance to demyelination. The role of the MHC in determining resistance or susceptibility to disease can be interpreted either as the presence of antigen-presenting molecules that confer resistance to viral infection or as the ability of MHC products to contribute to pathogenesis by acting as viral receptors or by mediating immune attack against virally infected cells. These alternatives can be distinguished by determining whether the contribution of the MHC to resistance is inherited as a recessive or dominant trait. Congenic mice with different MHC haplotypes on identical B10 backgrounds were crossed and quantitatively analyzed for demyelination, infectious virus, and local virus antigen production. F1 hybrid progeny derived from resistant B10 (H-2b), B10.D2 (H-2d), or B10.K (H-2k) and susceptible B10.R111 (H-2r), B10.M (H-2f), or B10.BR (H-2k) parental mice exhibited no or minimal demyelination...