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Kei Watanabe Kenta Wada Tomoko Ohashi Saki Okubo Kensuke Takekuma Ryoichi Hashizume Jun-Ichi Hayashi Tadao Serikawa Takashi Kuramoto Yoshiaki Kikkawa 《PloS one》2012,7(11)
We discovered a new cataract mutation, kfrs4, in the Kyoto Fancy Rat Stock (KFRS) background. Within 1 month of birth, all kfrs4/kfrs4 homozygotes developed cataracts, with severe opacity in the nuclei of the lens. In contrast, no opacity was observed in the kfrs4/+ heterozygotes. We continued to observe these rats until they reached 1 year of age and found that cataractogenesis did not occur in kfrs4/+ rats. To define the histological defects in the lenses of kfrs4 rats, sections of the eyes of these rats were prepared. Although the lenses of kfrs4/kfrs4 homozygotes showed severely disorganised fibres and vacuolation, the lenses of kfrs4/+ heterozygotes appeared normal and similar to those of wild-type rats. We used positional cloning to identify the kfrs4 mutation. The mutation was mapped to an approximately 9.7-Mb region on chromosome 7, which contains the Mip gene. This gene is responsible for a dominant form of cataract in humans and mice. Sequence analysis of the mutant-derived Mip gene identified a 5-bp insertion. This insertion is predicted to inactivate the MIP protein, as it produces a frameshift that results in the synthesis of 6 novel amino acid residues and a truncated protein that lacks 136 amino acids in the C-terminal region, and no MIP immunoreactivity was observed in the lens fibre cells of kfrs4/kfrs4 homozygous rats using an antibody that recognises the C- and N-terminus of MIP. In addition, the kfrs4/+ heterozygotes showed reduced expression of Mip mRNA and MIP protein and the kfrs4/kfrs4 homozygotes showed no expression in the lens. These results indicate that the kfrs4 mutation conveys a loss-of-function, which leads to functional inactivation though the degradation of Mip mRNA by an mRNA decay mechanism. Therefore, the kfrs4 rat represents the first characterised rat model with a recessive mutation in the Mip gene. 相似文献
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Human T-lymphoblastoid cell lines RPMI 8402, MOLT-3, and CCRF-CEM were treated with interferon (IFN) to determine if the treatment would result in the disappearance of cellular terminaldeoxynucleotidyltransferase (TdT), a possible differentiation marker for T-lymphocytes. Incubation of RPMI 8402 cells in the presence of IFN preparation caused a decrease in the number of TdT-positive cells and in TdT activity of the cell extract. The inhibition of cell multiplication was dose dependent. The anticellular effect of IFN preparation was cytostatic, not cytocidal. The IFN preparation modified neither the TdT content nor proliferation of MOLT-3 and CCRF-CEM cell lines. The effects of IFN preparation thus varied with the cell line. 相似文献
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Andoh Tomio; Itoh Hideki; Watanabe Itaru; Sasaki Toshio; Higashi Tomoko 《American journal of physiology. Cell physiology》2001,281(6):C1871
Substance P is known to modulate neuronal nicotinicacetylcholine receptors (nAChRs) in the sympathetic nervous system.There are two conflicting proposals for the mechanism of this effect, an indirect action mediated by protein kinase C (PKC) and a direct interaction with receptor subunits. We studied the mechanisms of thiseffect in PC-12 cells. Substance P enhanced the decay of thenicotine-induced whole cell current. This effect was fast in its onsetand was not antagonized by guanosine5'-O-(2-thiodiphosphate), a G protein blocker, orstaurosporine, a nonselective PKC blocker. Staurosporine failed toreverse the inhibition by 1-oleoyl-2-acetyl-sn-glycerol (OAG), a synthetic diacylglycerol analog known to activate PKC. Theinhibitory effects of the peptide and OAG were preserved in excisedpatches, but substance P applied to the extra patch membrane wasineffective in the cell-attached patch configuration. We conclude thatsubstance P modulates neuronal nAChRs most likely by direct interactions with the receptors but independently from activation ofPKC or G proteins and that PKC does not participate in modulation by OAG. 相似文献
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Modulation of brain progestin and glucocorticoid receptors by unsaturated fatty acid and phospholipid 总被引:1,自引:0,他引:1
J Kato A Takano N Mitsuhashi N Koike K Yoshida S Hirata 《Journal of steroid biochemistry》1987,27(4-6):641-648
In an attempt to learn how nonsteroidal factors modulate brain progestin and glucocorticoid receptors, the effects of saturated and unsaturated fatty acids, and phosphatidylinositol on the binding of [3H]R5020 or [3H]dexamethasone, determined by sucrose density gradient and gel filtration on LH20, were examined in the cerebral cortical cytosol from 10-day-old female rats which contain a considerable amount of progestin and glucocorticoid receptors. Unsaturated fatty acids such as oleic (C18:1), arachidonic (C20:4) and docosahexaenoic acid (C22:4) depressed the [3H]R5020 or [3H]dexamethasone binding in increasing order, but saturated fatty acids had no effect. Arachidonic and docosahexaenoic acids, which were strong inhibitors, lowered the binding dose dependently. The fatty acid inhibition on brain progestin and glucocorticoid receptors was thus a function of acid dose and degree of acid unsaturation. Interestingly, prostaglandin D2 did not show any effect. Among phospholipids tested the inhibitory effect of phosphatidylinositol on the [3H]R5020 binding was evident, but no significant effect was found with phosphatidylethanolamine, phosphatidylcholine, phosphatidylserine or sphingomyelin. The phosphatidylinositol inhibition was dose dependent. Analysis on kinetics and Scatchard plot have revealed the noncompetitive type of inhibition by arachidonic acid and phosphatidylinositol. From these results it is suggested that the unsaturated nonestrified fatty acid, arachidonic acid, and phosphoinositides modulate the brain progestin and, possibly, glucocorticoid receptors through their binding at sites different from steroid binding sites on the respective receptor molecules. 相似文献
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Purification and characterization of erythroid differentiation factor (EDF) isolated from human leukemia cell line THP-1 总被引:23,自引:0,他引:23
Y Eto T Tsuji M Takezawa S Takano Y Yokogawa H Shibai 《Biochemical and biophysical research communications》1987,142(3):1095-1103
We isolated a protein, from a cell line of human origin, which exhibits extensive differentiation inducing activity toward Friend leukemia cells. The protein, called Erythroid Differentiation Factor (EDF), was found in a 4 day culture of THP-1 cells performed in the presence of 4 beta-phorbol 12-myristate 13-acetate(PMA). EDF is a homodimer of a molecular weight of 25,000, with an NH2-terminal sequence identical to that of the beta A-chain of porcine Inhibin. It was suggested that a single protein species is responsible for the activities of both EDF and FRP, a FSH releasing protein isolated from porcine ovarian follicular fluid. 相似文献
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Tomoko Ohta 《Genetics》1987,115(1):207-213
By considering the recent finding that unequal crossing over and other molecular interactions are contributing to the evolution of multigene families, a model of the origin of repetitive genes was studied by Monte Carlo simulations. Starting from a single gene copy, how genetic systems evolve was examined under unequal crossing over, random drift and natural selection. Both beneficial and deteriorating mutations were incorporated, and the latter were assumed to occur ten times more frequently than the former. Positive natural selection favors those chromosomes with more beneficial mutations in redundant copies than others in the population, but accumulation of deteriorating mutations (pseudogenes) have no effect on fitness so long as there remains a functional gene. The results imply the following: Positive natural selection is needed in order to acquire gene families with new functions. Without it, too many pseudogenes accumulate before attaining a functional gene family. There is a large fluctuation in the outcome even if parameters are the same. When unequal crossing over occurs more frequently, the system evolves more rapidly. It was also shown, under realistic values of parameters, that the genetic load for acquiring a new gene is not as large as J.B.S. Haldane suggested, but not so small as in a model in which a system for selection started from already redundant genes. 相似文献