Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P50583 (asymmetrical)
 12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two distinct bidirectional selective breedings for quantitative traits were initiated from identical genetically heterogeneous mouse populations. The resulting lines are characterized by maximal or minimal acute inflammatory responsiveness (AIR): AIRmax and AIRmin lines, respectively, and by resistance or susceptibility to chemical skin tumorigenesis: Car-R and Car-S lines, respectively. The AIR response to s.c. injection of polyacrylamide microbeads, measured by cell content in the local exudate, was 10 times higher in AIRmax than in AIRmin mice. The response to selection was asymmetrical: the realized heritability was 0.26 in AIRmax and 0.008 in AIRmin, and resulted from the additive effect of 7-11 quantitative trait loci (QTL). Low responsiveness was globally dominant in F1 and 48% of F2 segregant variance was found to be due to genetic factors. These findings are the first demonstration of innate regulation of AIR by germ line genes. Susceptibility to skin tumorigenesis induced by a two-stage initiation (DMBA)-promotion (TPA) protocol was lower in AIRmax mice than in AIRmin mice, a 6-fold difference in tumor induction rate. Intense AIR was found to be associated with resistance, and low AIR with susceptibility to tumorigenesis, in F2 segregants chosen for extreme AIR phenotypes. At least some of the AIR QTLs therefore contain genes controlling tumorigenesis. Tumor phenotypes differed more in Car-R and Car-S than in AIRmax and AIRmin lines, indicating that QTLs unrelated to AIR, contribute to the host response to tumorigenesis. The extreme phenotypes/genotypes of the four selected lines and the known genetic constitution of their foundation population, offer new possibilities to discriminate the genes/mechanisms controlling two important traits: AIR and response to chemical tumorigenesis. Collaborative projects will be favorably considered. The description of tumor resistance genes in AIRmax and Car-R mice may be helpful for epidemiology and therapy of human cancer.
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PMID:Effect of genetic modification of acute inflammatory responsiveness on tumorigenesis in the mouse. 949 86

The morphogenesis of the visual cells in the retina of DBA normal mice and in C3H mice having a genetic distrophy has been studied with the electron microscope. The stages of development previously described (3) have been confirmed. Two basal centrioles have been observed and an asymmetrical process of invagination of the surface membrane is recognized as the main source of the rod sacs in the outer segment. In the C3H mice the differentiation of the photoreceptors starts and reaches a certain stage but very early some alterations in the morphogenesis are observed. In the outer segment there appears a disorganized growth of membranous material that may invade the inner segment with disappearance of the normal connecting cilium. In the inner segment there is an increase of vesicular material and in the number of dense particles. In later stages the entire inner segment is filled with dense particles and the mitochondria degenerate. The synaptic junction with the bipolar cell, which reaches a certain degree of development, also shows early signs of degeneration. The observations reported have confirmed and extended the concept that the hereditary visual alterations of C3H mice are not the result of a primary arrested development but of a secondary alteration of the differentiating photoreceptor. In C3H mice the entire process of morphogenesis is disordered and leads to final involution and death. These findings are correlated with recent biochemical findings and are discussed with relation to the genetic mechanisms that may control normal morphogenesis.
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PMID:Submicroscopic analysis of the genetic distrophy of visual cells in C3H mice. 1441 24

Heparanase has been implicated in cancer but its contribution to the early stages of cancer development is uncertain. In this study, we utilized nontransformed human MCF10A mammary epithelial cells and two genetic mouse models [Hpa-transgenic (Hpa-Tg) and knockout mice] to explore heparanase function at early stages of tumor development. Heparanase overexpression resulted in significantly enlarged asymmetrical acinar structures, indicating increased cell proliferation and decreased organization. This phenotype was enhanced by coexpression of heparanase variants with a mutant H-Ras gene, which was sufficient to enable growth of invasive carcinoma in vivo. These observations were extended in vivo by comparing the response of Hpa-Tg mice to a classical two-stage 12-dimethylbenz(a)anthracene (DMBA)/12-o-tetradecanoylphorbol-13-acetate (TPA) protocol for skin carcinogenesis. Hpa-Tg mice overexpressing heparanase were far more sensitive than control mice to DMBA/TPA treatment, exhibiting a 10-fold increase in the number and size of tumor lesions. Conversely, DMBA/TPA-induced tumor formation was greatly attenuated in Hpa-KO mice lacking heparanase, pointing to a critical role of heparanase in skin tumorigenesis. In support of these observations, the heparanase inhibitor PG545 potently suppressed tumor progression in this model system. Taken together, our findings establish that heparanase exerts protumorigenic properties at early stages of tumor initiation, cooperating with Ras to dramatically promote malignant development.
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PMID:Heparanase cooperates with Ras to drive breast and skin tumorigenesis. 2497 Apr 82