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Results for “genetic modifiers”

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At least 793 records · Page 44Linked to original sources
PubMed2001

Transplants of cells genetically modified to express neurotrophin-3 rescue axotomized Clarke's nucleus neurons after spinal cord hemisection in adult rats.

To test the idea that genetically engineered cells can rescue axotomized neurons, we transplanted fibroblasts and immortalized neural stem cells (NSCs) modified to express neurotrophic factors into the injured spinal cord. The neurotrophin-3 (NT-3) or nerve growth factor (NGF) transgene was introduced into these cells using recombinant retroviral vectors containing an internal ribosome entry site (IRES) sequence and the beta-galactosidase or alkaline phosphatase reporter gene. Bioassay confirmed biological activity of the secreted neurotrophic factors. Clarke's nucleus (CN) axons, which project to the rostral spinal cord and cerebellum, were cut unilaterally in adult rats by T8 hemisection. Rats received transplants of fibroblasts or NSCs genetically modified to express NT-3 or NGF and a reporter gene, only a reporter gene, or no transplant. Two months postoperatively, grafted cells survived at the hemisection site. Grafted fibroblasts and NSCs expressed a reporter gene and immunoreactivity for the NGF or NT-3 transgene. Rats receiving no transplant or a transplant expressing only a reporter gene showed a 30% loss of CN neurons in the L1 segment on the lesioned side. NGF-expressing transplants produced partial rescue compared with hemisection alone. There was no significant neuron loss in rats receiving grafts of either fibroblasts or NSCs engineered to express NT-3. We postulate that NT-3 mediates survival of CN neurons through interaction with trkC receptors, which are expressed on CN neurons. These results support the idea that NT-3 contributes to long-term survival of axotomized CN neurons and show that genetically modified cells rescue axotomized neurons as efficiently as fetal CNS transplants.

Animals↗
PubMed2003

Animal models to detect allergenicity to foods and genetically modified products: workshop summary.

Respiratory allergy and allergy to foods continue to be important health issues. There is evidence to indicate that the incidence of food allergy around the world is on the rise. Current estimates indicate that approximately 5% of young children and 1-2% of adults suffer from true food allergy (Kagan 2003). Although a large number of in vivo and in vitro tests exist for the clinical diagnosis of allergy in humans, we lack validated animal models of allergenicity. This deficiency creates serious problems for regulatory agencies and industries that must define the potential allergenicity of foods before marketing. The emergence of several biotechnologically derived foods and industrial proteins, as well as their potential to sensitize genetically predisposed populations to develop allergy, has prompted health officials and regulatory agencies around the world to seek approaches and methodologies to screen novel proteins for allergenicity.

Animals↗
PubMed2005

Polymorphisms in exon 13 and intron 14 of the RET protooncogene: genetic modifiers of medullary thyroid carcinoma?

CONTEXT: Single-nucleotide polymorphisms (SNPs) of the RET protooncogene (RET) could modify disease susceptibility and clinical phenotype in patients with sporadic or familial medullary thyroid carcinoma (FMTC). OBJECTIVE/DESIGN OF THE STUDY: Because frequencies of RET SNPs have not yet been evaluated in patients with elevated serum concentrations of calcitonin (hCt), a biochemical marker for medullary thyroid carcinoma (MTC), we studied RET SNPs in patients with FMTC (n = 22), patients with sporadic MTC (n = 45), and 71 subjects presenting with moderately elevated hCt concentrations (basal, >10 pg/ml; pentagastrin stimulated, > 50 < 100 pg/ml) in comparison with an age- and gender-matched control group (n = 79) with basal hCt concentrations in the normal range (<5 pg/ml). METHODS: After DNA extraction from citrated whole blood, RET exons 10, 11, 13, 14, 15, and 16 and exon/intron boundaries were analyzed by PCR-based cycle sequencing for RET germ line mutations, exonic (G691S, L769L, S836S, S904S) and intronic (IVS13+158; NCBI rs2472737 = IVS14-24) SNPs. RESULTS: In FMTC patients, the F791Y mutation was found to be associated (P = 0.001) with the L769L SNP. The exonic SNPs (G691S, L769L, S836S, and S904S) were not different among the four groups. The intron 14 SNP (IVS14-24), however, was more frequent in individuals with elevated hCt serum concentrations (P = 0.016) and patients with sporadic MTC (P < 0.001) when compared with the control group. CONCLUSIONS: These data suggest that the exon 13 (L769L) and the intron 14 (IVS14-24) SNPs could act as genetic modifiers in the development of some forms of hereditary and sporadic MTC, respectively.

Adult↗
PubMed2006

Cytolytic and cytotoxic activity of a human natural killer cell line genetically modified to specifically recognize HER-2/neu overexpressing tumor cells.

NK92 cells genetically engineered to recognize the HER-2/neu oncoprotein have been previously reported to lyse HER-2/neu positive tumor cell lines through direct cell to cell contact. In the present study we have transduced NK92 cells with a chimeric receptor gene composed of the HER-/neu specific scFv (FRP5) antibody fragment, joined to the peptide CD8 hinge region and the signaling CD3 zeta chain. NK92 cells expressing this chimeric receptor (NK92.HER-2/neu/zeta) specifically recognized and lysed HER-2/neu overexpressing tumor cell lines both in vitro and in preclinical tumor models in vivo. More important we demonstrate that NK92.HER-2/neu/zeta cells constitutively secrete high levels of soluble scFv which mediate strong tumor cytostatic effects by directly binding on cell surface HER-2/neu. Our data uncover an additional mechanism through which NK92.HER-2/neu/zeta cells mediate antitumor effects and further support their use in cell based therapeutics for the treatment of HER-2/neu expressing cancers.

Animals↗
PubMed2004

DNA separation by capillary electrophoresis with hydrophilic substituted celluloses as coating and sieving polymers. Application to the analysis of genetically modified meals.

A coating procedure based on the physical adsorption of hydroxypropyl cellulose onto the wall of a capillary column has been successfully used for the separation of DNA fragments up to 500 bp. The method uses a running Tris-phosphate-EDTA buffer containing 2-hydroxyethyl cellulose as sieving polymer. The separation procedure shows good reproducibility (measured as RSD%) for consecutive runs (<0.64), for different days (< 1.15) and capillaries (<2.15), short analysis times, and a long coating lifetime. Good reproducibility and efficiency are even achieved by performing the separation in the presence of additives such as ethidium bromide and mannitol. The method is applied to the detection of GMOs in soybean and maize meals with an accurate evaluation of the length of DNA sequences, previously amplified by polymerase chain reaction.

Adsorption↗
PubMed2005

Risk mitigation of genetically modified bacteria and plants designed for bioremediation.

While the possible advantages of bioremediation and phytoremediation, by both recombinant microbes and plants, have been extensively reviewed, the biosafety concerns have been less extensively treated. This article reviews the possible risks associated with the use of recombinant bacteria and plants for bioremediation, with particular emphasis on ways in which molecular genetics could contribute to risk mitigation. For example, genetic techniques exist that permit the site-specific excision of unnecessary DNA, so that only the transgenes of interest remain. Other mechanisms exist whereby the recombinant plants or bacteria contain conditional suicide genes that may be activated under certain conditions. These methods act to prevent the spread and survival of the transgenic bacteria or plants in the environment, and to prevent horizontal gene flow to wild or cultivated relatives. Ways in which these genetic technologies may be applied to risk mitigation in bioremediation and phytoremediation are discussed.

Animals↗
PubMed2003

Creating genetically modified pigs by using nuclear transfer.

Nuclear transfer (NT) is a procedure by which genetically identical individuals can be created. The technology of pig somatic NT, including in vitro maturation of oocytes, isolation and treatment of donor cells, artificial activation of reconstructed oocytes, embryo culture and embryo transfer, has been intensively studied in recent years, resulting in birth of cloned pigs in many labs. While it provides an efficient method for producing transgenic pigs, more importantly, it is the only way to produce gene-targeted pigs. So far pig cloning has been successfully used to produce transgenic pigs expressing the green fluorescence protein, expand transgenic pig groups and create gene targeted pigs which are deficient of alpha-1,3-galactosyltransferase. The production of pigs with genetic modification by NT is now in the transition from investigation to practical use. Although the efficiency of somatic cell NT in pig, when measured as development to term as a proportion of oocytes used, is not high, it is anticipated that the ability of making specific modifications to the swine genome will result in this technology having a large impact not only on medicine but also on agriculture.

Animals↗