Podcasts about c3h

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Latest podcast episodes about c3h

Medizin - Open Access LMU - Teil 16/22
N-ethyl-N-nitrosourea mutagenesis produced a small number of mice with altered plasma electrolyte levels

Medizin - Open Access LMU - Teil 16/22

Play Episode Listen Later Jan 1, 2009


Background: Clinical chemical blood analysis including plasma electrolytes is routinely carried out for the diagnosis of various organ diseases. Phenotype-driven N-ethyl-N-nitrosourea (ENU) mouse mutagenesis projects used plasma electrolytes as parameters for the generation of novel animal models for human diseases. Methods: Here, we retrospectively evaluated the use of the plasma electrolytes calcium, chloride, inorganic phosphorus, potassium and sodium in the Munich ENU mouse mutagenesis project where clinical chemical blood analysis was carried out on more than 20,000 G1 and G3 offspring of chemically mutagenized inbred C3H mice to detect dominant and recessive mutations leading to deviations in various plasma parameter levels. Results: We identified a small number of animals consistently exhibiting altered plasma electrolyte values. Transmission of the phenotypic deviations to the subsequent generations led to the successful establishment of mutant lines for the parameters calcium and potassium. Published data from other phenotype-driven ENU projects also included only a small number of mutant lines which were generated according to altered plasma electrolyte levels. Conclusion: Thus, use of plasma electrolytes detected few mouse mutants in ENU projects compared to other clinical chemical blood parameters.

Tierärztliche Fakultät - Digitale Hochschulschriften der LMU - Teil 03/07
Histologische und molekulargenetische Untersuchungen von strahleninduzierten Schilddrüsentumoren im Mausmodell

Tierärztliche Fakultät - Digitale Hochschulschriften der LMU - Teil 03/07

Play Episode Listen Later Jul 20, 2007


Thyroid cancer derived from follicular epithelial cells is the most common endocrine malignancy in man. An increased incidence of predominantly papillary thyroid carcinomas (PTC) was found in children exposed to radiation after the Chernobyl nuclear accident in 1986. Therefore, in this study, the goal was to establish a mouse model of thyroid carcinogenesis, based on a standardized histological classification scheme for the murine thyroid tumors, and complemented by molecular genetic analyses. In previous studies, radioiodine (I131, 111 kBq) was injected into iodine deficient fed mothers of various mouse strains (F1-hybrids and backcrosses of C57/BL6, C3H, BALB/c, and JF1). The first injection was applied during gestation and the second during lactation. The necropsy tissue was submitted for the analysis in this study. A set of 365 thyroid glands (203 irradiated and 162 control mice) was histological examined following the current WHO classification of human thyroid tumors (2004) for comparative purposes. The irradiated mice showed 24 % of cases with simple hyperplasia (SH), 20 % with nodular hyperplasia (NH), 7 % with follicular thyroid adenoma (FTA), and 5 % with follicular thyroid carcinoma (FTC) whereas in the control group only 3 % SH, 3 % of NH, 1 % of FTA, and 1 % of FTC were observed. Interestingly, no PTC was diagnosed in the mice, which is the most frequent irradiation-related type of thyroid cancer in human. Therefore, the histological type of the radiation-associated thyroid tumors in mice differs from that in human. However, some cases of murine FTC presented PTC-like biological behavior. In addition to the significant increase of hyperplasias in irradiated mice, most of the FTC (82 %) arose amongst a background of hyperplastic nodules. Therefore, a progression from NH to FTC, based on genetic instability, cannot be ruled out. The following molecular methods were used: PCR- (polymerase chain reaction-) based loss of heterozygosity (LOH), comparative genomic hybridization (CGH), and fluorescence-in-situ-hybridization (FISH). Since the CGH-study in mice using formalin-fixed paraffin-embedded tissue (FFPE) is not yet established, an important part of the study was dedicated to evaluate this methodology. The LOH-study was performed with thyroid gland tissue from 40 mice (seven normal thyroid glands, 12 SH, 10 NH, 10 FTA, and one FTC) using 36 microsatellites for nine different loci. With the exception of an LOH with a single microsatellite on chromosome 14 in 40 % of NH, LOH was found in 75 % of the irradiated male mice with H6F1-background on chromosomes 4, 5, 6, 11, 14, and / or 19. This suggests the existence of a mouse strain specific genetic predisposition, which influence on the genetic stability. One of the FTA (an atypical FTA) was highly suspicious for a deletion of the tumorsuppressorgene Rb1 (supported by intragenic FISH-analysis), which could play an important role in the thyroid carcinogenesis. For the CGH-study, thyroid tissue derived from 21 different mice (F2-hybrids) was analyzed (two normal thyroid glands, one SH, 12 NH, two FTA, and eight FTC). In 46 % of the hyperplasias, small chromosomal gains and losses located on different chromosomes were observed; suggesting that there exists a genetic instability, which may lead eventually to malignant progression. Regional polyploidies on chromosomes 4 and 5 were demonstrated in one of the FTAs, which could be a hint for the location of oncogenes. Taken together, in FTA development there is a broad spectrum of genetic alteration, and by inference mechanisms. In contrast, the FTC exhibited a significant increase of specific aneuploidies, mainly deletions of the chromosomes 4 (88 %), 9 (50 %), and 14 (38 %). Identical alterations of chromosomes 4 and 9 were also observed in the one case of an FTC from a non-irradiated mouse. These data indicate that irradiation, most probably, increases the frequency of genetic changes, but does not change the type of genetic alterations, which play a crucial role in thyroid carcinogenesis in mice. A better understanding of molecular genetics involved in thyroid tumorigenesis in standardized mouse models may give insight into the pathogenesis of the various tumor types. Together with the results from human pathology and in vitro studies, this may lead to a better knowledge about the molecular pathways with diagnostic, prognostic, and therapeutic relevance. The results of this study demonstrate a morphological and genetical difference between human (PTC) and murine (FTC) radiation-associated thyroid tumors, but a strong similarity to the human follicular tumors. Therefore, this mouse model serves as a good model of carcinogenetic mechanisms, tumor induction, and progression in the human follicular tumors FTA and FTC, resulting from the cooperative effect of radioiodine exposition and iodine deficiency.

Tierärztliche Fakultät - Digitale Hochschulschriften der LMU - Teil 01/07
Phänotypische und genotypische Charakterisierung der ENU-induzierten Mausmutante HST001 zur Verwendung für die nephrologische Forschung

Tierärztliche Fakultät - Digitale Hochschulschriften der LMU - Teil 01/07

Play Episode Listen Later Feb 13, 2004


Phenotypic and genotypic characterization of the ENU-induced mutant mouse line HST001 for use in nephrological research A dominant mutation was established in the line HST001 within the Munich ENU mouse mutagenesis project. On the genetic background of the inbred strain C3H heterozygous mutant mice showed a pathological increase of the plasma urea concentration. The phenotypic characterization of the mutant line included the measurement of body and organ weights, food intake and a broad spectrum of clinical chemical and hematological parameters as well as histological investigations of inner organs. For those examinations heterozygous mutant mice were mated to C3H mice and the offspring were divided in the two groups of mutant and wildtype littermates according to the concentration of plasma urea. The mutation showed complete phenotypic penetrance in all generations examined. In addition the genomic localization of the causative mutation was determined by linkage analysis. At the age of 4 weeks the body weight of the mutant mice and the wildtype mice showed no difference. After 6 weeks the mutant mice grew more slowly leading to a significantly lower body weight compared to the wildtype littermates. At the age of 26 weeks the body weight of mutant mice was about 20% reduced as compared to controls. Mutants also showed a reduction of the nose-rump-length and the body fat content. Regarding the relative organ weights the mutant mice showed significantly higher values for the spleen and the brain. The clinical-chemical and hematological parameters were determined in the animals at the age of 12, 18 and 24 weeks. The mutant mice had significantly higher plasma concentrations of urea and total protein as well as a higher activity of the alkaline phosphatase. Beside that they showed lower plasma concentrations of triglycerides and glucose and a lower activity of amylase than the wildtype mice. The mutants showed increasing plasma urea levels whereas the levels decreased in the controls. At the age of 24 weeks the mutants showed levels, which were two-fold higher than those of the controls. The histopathological investigation of the kidneys did not reveal any alterations, which could to explain the pathological increase of the plasma urea concentration in the mutant mice. However urea secretion via the kidneys was impaired, since the mutants showed significantly lower urine urea levels compared to the wildtype mice. The investigation of the hematological parameters resulted in the occurrence of altered values in the 18 und 24 weeks old mice. The mutant mice showed reduced numbers 91 of erythrocytes as well as decreased values for hemoglobin concentration, mean corpuscular volume and hematocrit. The hitherto existing results of the linkage analysis of the mutation in the genome using polymorphic microsatellite markers showed that the mutation maps to chromosome 7. This result has to be confirmed and specified by using additional markers and a larger number of animals.

Tierärztliche Fakultät - Digitale Hochschulschriften der LMU - Teil 01/07
Phänotypische und genotypische Charakterisierung der ENU-induzierten Mausmutante SMA002 als Tiermodell für Wachstumsdefizit und Hyperaktivität

Tierärztliche Fakultät - Digitale Hochschulschriften der LMU - Teil 01/07

Play Episode Listen Later Feb 13, 2004


This thesis describes the phenotypic and genotypic analysis of the dominant mutation in the ENU-induced mutant mouse line SMA002. The results were derived from the analysis of heterozygous mutant animals on the C3H genetic background. As the main phenotype of SMA002, an abnormal behavior combined with reduced body weight was revealed. The mutant phenotype showed complete penetrance in all generations analyzed. Abnormal behavior, as the most prominent phenotype was characterized by the occurrence of restlessness and an increased grooming behavior. The grooming behavior was increased fivefold but did not always contain all aspects of the standard repertoire. Pathological examinations of the skin and the analysis of parameters of the immune system indicated that this behavior was not caused by an allergic reaction. Clinical examination of the animals revealed a significant difference in body weight between mutant and control littermates. The body weight of the mutant animals was about 30% lower than control. In addition mutant animals had a significant lower nose-rump length and a significant lower carcass weight. Analysis of the peripheral blood for hematological and clinical chemical parameters as well as subsequent pathological examinations excluded a kidney, liver or pancreas disease as the potential cause of the abnormal phenotype. Decreased values for cholesterol, triglyceride, total protein and potassium in the mutant animals referred to an increased metabolism and a hormonal deviation in these mice. Furthermore, deviations of the IGF-system were found in the mutants. Linkage analysis of the causative mutation was carried out by genome wide polymorphic microsatellite marker analysis. The highest correlation for the mutation was found with the markers D13Mit20 (35cM) and D13Mit253 (37cM) of chromosome 13. This aberrant phenotype of the line SMA002 has not yet been reported. Thus, SMA002 represents a novel mouse model for the analysis of abnormal behavior and growth defects. Subsequent analysis will identify the exact mutation in the line. In addition, further analysis of the phenotype will result in detailed information on the metabolism and hormonal regulation of SMA002.

Medizin - Open Access LMU - Teil 04/22
The influence of timeshift on ciradian rhythm of sensitivity to X-irradiation in mice

Medizin - Open Access LMU - Teil 04/22

Play Episode Listen Later Jan 1, 1984


For two groups of male C3H mice an eastbound transmeridional flight was simulated by inducing a time shift of the L:D schedule of 8 hr. The assumed flight brought about a maxima) reduction of the daily light and dark span, respectively. A third group remained unshifted. At seven different times during the following day, subgroups of the time shifted mice as well as of the group with unchange schedule were exposed to whole body X-irradiation. Mortality and body temperature of each animal were registered for 30 days following exposure and were regarded as indicators of radiation response. Radioresistance was found to be highest during the second half of the daily light span, confirming earlier reports by other authors. Well defined effects of the time shift and a corresponding shift of the acrophase of radioresistance could be demonstrated. There was no significant difference between the two time shifted groups, but there was a consistent slight trend towards an advantage for the group whose L:D shift resulted in a maximally reduced dark span.

Medizin - Open Access LMU - Teil 03/22
Involvement of Mhc Loci in immune responses that are not Ir-gene-controlled

Medizin - Open Access LMU - Teil 03/22

Play Episode Listen Later Jan 1, 1982


Twenty-nine randomly chosen, soluble antigens, many of them highly complex, were used to immunize mice of two strains, C3H and B10.RIII. Lymphnode cells from the immunized mice were restimulated in vitro with the priming antigens and the proliferative response of the cells was determined. Both strains were responders to 28 of 29 antigens. Eight antigens were then used to immunize 11 congenic strains carrying different H-2 haplotypes, and the T-cell proliferative responses of these strains were determined. Again, all the strains responded to seven of the eight antigens. These experiments were then repeated, but this time -antibodies specific for the A (AA) or E (EE) molecules were added to the culture to block the in vitro responsiveness. In all but one of the responses, inhibition with both A-specific and E-specific antibodies was observed. The response to one antigen (Blastoinyces) was exceptional in that some strains were nonresponders to this antigen. Furthermore, the response in the responder strains was blocked with A-specific, but not with E-specific, antibodies. The study demonstrates that responses to antigens not controlled by Irr genes nevertheless require participation of class II Mhc molecules. In contrast to Ir gene-controlled responses involving either the A- or the E-molecule controlling loci (but never both), the responses not Ir-controlled involve participation of both A- and E-controlling loci. The lack of Ir-gene control is probably the result of complexity of the responses to multiple determinants. There is thus no principal difference between responses controlled and those not controlled by Ir genes: both types involve the recognition of the antigen, in the context of Mhc molecules.

Medizin - Open Access LMU - Teil 02/22
Lysis mediated by T cells and restricted by H-2 antigen of target cells infected with vaccinia virus

Medizin - Open Access LMU - Teil 02/22

Play Episode Listen Later Jan 1, 1975


VARIOUS virus infections lead to the formation of cytotoxic lymphocytes (CL), which are capable of killing virus-infected target cells1−4. Specific lysis of target cells infected with 51Cr-labelled vaccinia virus could be observed when investigating the cell-mediated cytotoxic reaction to vaccinia virus5; the CL could be characterised as a T cell. The sensitised lymphocytes from C3H mice could only kill syngeneic L929 cells infected with vaccinia virus, whereas lysis by sensitised lymphocytes derived from DBA/2 mice was restricted to the syngeneic infected mastocytoma P815X2 cells. In the lymphocytic choriomeningitis infection the target cell lysis was shown to be restricted by H-2 antigen6. We report here experiments with primary fibroblasts of the mouse strains C3H, DBA/2 and the (C3H DBA/2)F1 generation were designed to affirm that the effector phase of virus-specific lysis of target cells mediated by T cells is restricted by H-2 antigen even in the vaccinia virus infection. Further experiments with H-2 alloantisera were performed to indicate the close local relationship between H-2 antigens and viral surface antigens.

Medizin - Open Access LMU - Teil 02/22
Target cell-dependent T cell-mediated lysis of vaccinia virus-infected cells

Medizin - Open Access LMU - Teil 02/22

Play Episode Listen Later Jan 1, 1975


Vaccinia virus specific cytotoxicity against infected target cells was observed in vitro. Spleen lymphocytes from normal and immunized mice of the inbred strains C3H and DBA/2 were incubated with vaccinia virus-infected and non-infected 51Cr-labeled mastocytoma P-815-X2 cells and L-929 fibroblasts, which were used as targets. Cytotoxic lymphocytes could be isolated from the mice as early as 2 days after infection with vaccinia virus. The highest cytotoxic effect was obtained with lymphocytes taken 6 days after infection. The degree of lysi was correlated with the ratio of immune lymphocytes to target cells. Specific blocking of target cell lysis resulted after addition of anti-vaccinia antibody from different sources. The effector cells could be characterized as T cells by elimination of macrophages and B cells. Target cell killing was only possible in a syngeneic system; allogeneic infected target cells were not lysed significantly.