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We previously reported that aged mice lacking complement factor H (CFH) exhibit visual defects and structural changes in the retina. However, it is not known whether this phenotype is age-related or is the consequence of disturbed development. To address this question we investigated the effect of Cfh gene deletion on the retinal phenotype of young and mid-age mice. Cfh
−/− mouse eyes exhibited thickening of the retina and reduced nuclear density, but relatively normal scotopic and photopic electroretinograms. At 12 months there was evidence of subtle astroglial activation in the Cfh
−/− eyes, and significant elevation of the complement regulator, decay-accelerating factor (DAF) in Müller cells. In the retinal pigment epithelium (RPE) of young control and Cfh
−/− animals mitochondria and melanosomes were oriented basally and apically respectively, whereas the apical positioning of melanosomes was significantly perturbed in the mid-age Cfh
−/− RPE. We conclude that deletion of Cfh in the mouse leads to defects in the retina that precede any marked loss of visual function, but which become progressively more marked as the animals age. These observations are consistent with a lifelong role for CFH in retinal homeostasis. 相似文献
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Magni Olsen Kyrkjeeide Kristian Hassel Kjell Ivar Flatberg A. Jonathan Shaw Narjes Yousefi Hans K. Sten?ien 《PloS one》2016,11(2)
Spore-producing organisms have small dispersal units enabling them to become widespread across continents. However, barriers to gene flow and cryptic speciation may exist. The common, haploid peatmoss Sphagnum magellanicum occurs in both the Northern and Southern hemisphere, and is commonly used as a model in studies of peatland ecology and peatmoss physiology. Even though it will likely act as a rich source in functional genomics studies in years to come, surprisingly little is known about levels of genetic variability and structuring in this species. Here, we assess for the first time how genetic variation in S. magellanicum is spatially structured across its full distribution range (Northern Hemisphere and South America). The morphologically similar species S. alaskense was included for comparison. In total, 195 plants were genotyped at 15 microsatellite loci. Sequences from two plastid loci (trnG and trnL) were obtained from 30 samples. Our results show that S. alaskense and almost all plants of S. magellanicum in the northern Pacific area are diploids and share the same gene pool. Haploid plants occur in South America, Europe, eastern North America, western North America, and southern Asia, and five genetically differentiated groups with different distribution ranges were found. Our results indicate that S. magellanicum consists of several distinct genetic groups, seemingly with little or no gene flow among them. Noteworthy, the geographical separation of diploids and haploids is strikingly similar to patterns found within other haploid Sphagnum species spanning the Northern Hemisphere. Our results confirm a genetic division between the Beringian and the Atlantic that seems to be a general pattern in Sphagnum taxa. The pattern of strong genetic population structuring throughout the distribution range of morphologically similar plants need to be considered in future functional genomic studies of S. magellanicum. 相似文献
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The effects of luteinizing hormone-releasing hormone (LRH) and thyrotropin-releasing hormone (TRH) upon the lordotic response to repetitive coital stimlation were studied using ovariectomized (OVX) and ovariectomized-adrenalectomized (OVX-ADX) female rats. Both OVX and OVX-ADX rats, pretreated with estrone alone, exhibited a dual behavioral response to repeated coital stimulation. The initial response to short-term stimulation was facilitatory with peak sexual receptivity occurring approximately 120 min following the initial male contact. This initial phase was followed by a depression of sexual receptivity associated with continued coital stimulation. Subcutaneous injection of 500 ng of LRH prior to mating was found to significantly potentiate the initial increases in sexual receptivity and to delay the onset of behavioral depression. The injection of 500 ng of TRH was observed to significantly depress behavioral enhancement due to repetitive coital stimulation.The repetitive coital stimulation model was utilized to localize forebrain areas behaviorally responsive to LRH and TRH. Stainless steel cannulas were implanted into either the medial preoptic area (MPOA), arcuate area (ARC), lateral hypothalamic area (LHA), or cerebral cortex (CC). Cannulated animals, primed with estrone, were tested for sexual receptivity immediately prior to experimental treatment, i.e., the infusion of 0.5 μl of 50 ng of LRH or TRH in 0.9% saline, 0.5 μl of 0.9% saline, or sham infusion. A second mating (postinfusion) test was performed 1.75 hr following infusion. When infused into the MPOA or ARC, LRH significantly enhanced lordotic behavior as compared to values obtained for saline or sham infusions. The infusion of LRH into LHA or CC showed no enhancement beyond the levels observed in control infusions (saline and sham infusions). The infusion of TRH into the MPOA or ARC depressed lordotic enhancement to repeated mating, however, this depression was significant only in ARC. These findings were consistent with previously demonstrated actions of releasing hormones upon neural activity within the MPOA and ARC. 相似文献
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Pro-opiomelanocortin (POMC) was expressed in CV-1 (green monkey kidney) cells using a vaccinia virus transient expression system [(1986) Proc. Natl. Acad. Sci. USA 83, 8122]. The system involved infection of cells with a recombinant vaccinia virus carrying the T7 RNA polymerase gene and transfection with a plasmid containing the mouse POMC sequence flanked by the T7 RNA polymerase promoter at its 5'-end and the T7 RNA polymerase terminator at its 3'-end. Assay of the medium from transfected cells showed that 1-2 micrograms of immunoreactive ACTH was produced/10(6) cells. Analysis of the same medium by SDS-PAGE/Western blots revealed a band of 30-36 kDa, which was immunostained with both ACTH and beta-endorphin antisera. Labeling the transfected cells with [3H]Arg, followed by immunoprecipitation and SDS-PAGE showed the synthesis of a major peak of POMC, 33 kDa. Purified [3H]POMC expressed by CV-1 cells was cleaved in vitro by bovine intermediate lobe secretory vesicle pro-opiomelanocortin-converting enzyme to ACTH intermediates (19-25 kDa), beta-lipotropin and beta-endorphin. Thus, this work has demonstrated a technique for expressing microgram quantities of prohormones in mammalian cells, suitable for use as substrates for prohormone-converting enzymes in vitro. 相似文献
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