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PubMed1999

Environmental monitoring of genetically modified crops.

Genetically modified (GM) crops are now approved for commercial use in several world areas. In terms of commercial acreage, the majority of these products possess either herbicide tolerance or insect protection traits. Prior to commercialization, each product underwent a country specific review of environmental safety data by independent regulatory authorities. Registration was granted after review of the data allowed authorities to conclude that the risks were minimal or manageable when balanced with the benefits. As a condition of registration, insect resistance management (IRM) has been imposed for insect protected products in most countries. Other world areas have reviewed similar data packages and have not yet been able to grant registration for commercial release. Post-registration environmental monitoring of GM crops is viewed in some world areas as a means of enabling approvals by addressing uncertainty that exists with this technology. Questions such as, who should monitor and who should pay for it, how should monitoring be conducted, what information is necessary to collect and how long should a given product be monitored are yet to be answered. Monitoring methods could be general (surveys and questionnaires) or specific (scientific studies to address specific questions). Independent research currently underway in countries where GM crops are commercial involves monitoring the benefits as well as the risks of these products. Experience with other products has shown that monitoring of GM crops will be of value only if the questions are clearly defined, the methods are appropriate and the end points (data collected) are interpretable.

Agriculture↗
PubMed2005

In vivo characterization of skeletal phenotype of genetically modified mice.

Genetically modified mouse models provide an important tool for understanding of the roles of specific gene in skeletal growth, development, and aging. Appropriate study design is essential for characterization of skeletal phenotype of these mice. It is important to characterize the bone status of the different phases of skeletal development including the early rapid growth, attainment of peak bone mass, and age-related bone loss phases. In C57BL/6 strain mice, cancellous and cortical bone mass rapidly increases with age before 3 months of age, and reaches the peak cancellous bone mass at approximately 6-8 months of age, while cortical bone mass continuously increases until 12 months of age. Thereafter, age-related decrease in bone mass occurs. According to these observations, at least three different age groups need to be evaluated for bone status to cover the different phases of the life span: 1-3 months of age for rapid growth, 6-9 months for peak bone mass, and >12 months for aged phases. Furthermore, bone resorption and formation activities on all bone surfaces (periosteal, endocortical, intracortical, and cancellous) need to be evaluated. In this article, we briefly summarize our findings in the estrogen receptor-beta knockout (BERKO) and the P2X7 receptor (an ATP-gated ion channel) knockout mice. In BERKO female mice, bone status at 6, 13, and 21 months of ages was evaluated as compared with the wild-type littermate controls. We found that estrogen receptor-beta plays an inhibitory role in periosteal bone formation and longitudinal and radial growth during the growth period, whereas it plays a role in stimulation of bone resorption, bone turnover, and bone loss on cancellous and endocortical bone surfaces during the aging process. We also found that ER-beta knockout improves the survival rate between 6 and 21 months of age. In P2X7R knockout mice, bone status at 2, 5, 9, and 15 months of age was evaluated for both sexes as compared with their wild-type littermate controls. We found that P2X7R plays a role in stimulating periosteal and cancellous bone formation and inhibiting cancellous bone resorption during the growth period.

Aging↗
PubMed2005

Animal nutrition with feeds from genetically modified plants.

Plant breeders have made and will continue to make important contributions toward meeting the need for more and better feed and food. The use of new techniques to modify the genetic makeup of plants to improve their properties has led to a new generation of crops, grains and their by-products for feed. The use of ingredients and products from genetically modified plants (GMP) in animal nutrition properly raises many questions and issues, such as the role of a nutritional assessment of the modified feed or feed additive as part of safety assessment, the possible influence of genetically modified (GM) products on animal health and product quality and the persistence of the recombinant DNA and of the 'novel' protein in the digestive tract and tissues of food-producing animals. During the last few years many studies have determined the nutrient value of GM feeds compared to their conventional counterparts and some have additionally followed the fate of DNA and novel protein. The results available to date are reassuring and reveal no significant differences in the safety and nutritional value of feedstuffs containing material derived from the so-called 1st generation of genetically modified plants (those with unchanged gross composition) in comparison with non-GM varieties. In addition, no residues of recombinant DNA or novel proteins have been found in any organ or tissue samples obtained from animals fed with GMP. These results indicate that for compositionally equivalent GMP routine-feeding studies with target species generally add little to nutritional and safety assessment. However, the strategies devised for the nutritional and safety assessment of the 1st generation products will be much more difficult to apply to 2nd generation GMP in which significant changes in constituents have been deliberately introduced (e.g., increased fatty acids or amino acids content or a reduced concentration of undesirable constituents). It is suggested that studies made with animals will play a much more important role in insuring the safety of these 2nd generation constructs.

Animal Feed↗
PubMed2002

Welfare issues of genetically modified animals.

Genetically engineered animals have opened new frontiers in the study of physiology and disease processes. Mutant animals offer more accurate disease models and increased precision for pathogenesis and treatment studies. Their use offers hope for improved therapy to patients with conditions that currently have poor or ineffective treatments. These advantages have fostered an increase in studies using mice in recent years, a development viewed with alarm by those who oppose the use of animals in research. Scientists point out that the mice are replacing more sentient species, such as nonhuman primates, and are increasing the quality of research being conducted. They assert that study of genetically engineered animals will eventually permit decreases in numbers of animals used in research. Nevertheless, the increase in use of genetically altered animals presents many challenges in reviewing protocols and providing care. Identification and resolution of any welfare problems is a responsibility that is shared by institutional animal care and use committee, veterinary, animal care, and research staffs. To identify potential welfare concerns, a database such as TBASE ( ) can be searched to learn what has been reported for established mutant lines. In addition, newly created lines should be monitored by a surveillance system and have phenotype assessment to identify the effects of altering the genome. Methods of ensuring welfare can include treatment of conditions produced, restriction of gene expression to tissues of interest or to certain time periods, and establishment of endpoints for removing animals from a study before problems appear.

Animal Husbandry↗
PubMed2005

New considerations in infectious disease outbreaks: the threat of genetically modified microbes.

Genetically altered microbes are used widely in the conduct of scientific study and have facilitated the development of new medical therapies, preventive strategies, and diagnostic tools. Unfortunately, such organisms may also cause infectious disease outbreaks as a result of accidental or intentional transmission to humans. The unique microbial properties of genetically altered pathogens and the clinical symptoms exhibited by persons infected with them may impede the usual diagnostic and clinical evaluations or preventive strategies. Practicing physicians and clinicians at microbiology laboratories, who would be the first to observe such infections, must consider the broad clinical possibilities of illnesses caused by deliberately altered microorganisms and the potential difficulty in confirming a diagnosis.

Bacterial Infections↗
PubMed2003

[Nutrition and health--genetically modified food].

The genetically modified (GM) crops cultivated at present have new properties of benefit to agriculture. It is expected that in the future GM crops will also be cultivated with more complex genetic modifications that are aimed at improving the nutritional and health value to the consumer. The safety assessment of GM foods before market approval is based on a comparison of the characteristics of the GM food with those of the conventional counterpart. Identified differences are thoroughly tested for their toxicological and nutritional consequences. Supplementary modern analytical techniques are being developed for the assessment of future complex GM foods. No cases of adverse health or nutritional effects in consumers have been reported for the existing generation of GM foods. The feasibility of post-market surveillance of (GM) foods, in order to identify small or chronic effects that have not been noticed in the pre-market phase, is being investigated, yet its value should not be overestimated. Surveillance can be informative in case of specific questions concerning certain products as long as the consumer intake is well documented. To this end traceability and labelling systems must be set up.

Consumer Behavior↗
PubMedDate not supplied

Real-time polymerase chain reaction detection of cauliflower mosaic virus to complement the 35S screening assay for genetically modified organisms.

Labeling of genetically modified organisms (GMOs) is now in place in many countries, including the European Union, in order to guarantee the consumer's choice between GM and non-GM products. Screening of samples is performed by polymerase chain reaction (PCR) amplification of regulatory sequences frequently introduced into genetically modified plants. Primers for the 35S promoter from Cauliflower mosaic virus (CaMV) are those most frequently used. In virus-infected plants or in samples contaminated with plant material carrying the virus, false-positive results can consequently occur. A system for real-time PCR using a TaqMan minor groove binder probe was designed that allows recognition of virus coat protein in the sample, thus allowing differentiation between transgenic and virus-infected samples. We measured the efficiency of PCR amplification, limits of detection and quantification, range of linearity, and repeatability of the assay in order to assess the applicability of the assay for routine analysis. The specificity of the detection system was tested on various virus isolates and plant species. All 8 CaMV isolates were successfully amplified using the designed system. No cross-reactivity was detected with DNA from 3 isolates of the closely related Carnation etched ring virus. Primers do not amplify plant DNA from available genetically modified maize and soybean lines or from different species of Brassicaceae or Solanaceae that are natural hosts for CaMV. We evaluated the assay for different food matrixes by spiking CaMV DNA into DNA from food samples and have successfully amplified CaMV from all samples. The assay was tested on rapeseed samples from routine GMO testing that were positive in the 35S screening assay, and the presence of the virus was confirmed.

Base Sequence↗
PubMed2004

In search of a depressed mouse: utility of models for studying depression-related behavior in genetically modified mice.

The ability to modify mice genetically has been one of the major breakthroughs in modern medical science affecting every discipline including psychiatry. It is hoped that the application of such technologies will result in the identification of novel targets for the treatment of diseases such as depression and to gain a better understanding of the molecular pathophysiological mechanisms that are regulated by current clinically effective antidepressant medications. The advent of these tools has resulted in the need to adopt, refine and develop mouse-specific models for analyses of depression-like behavior or behavioral patterns modulated by antidepressants. In this review, we will focus on the utility of current models (eg forced swim test, tail suspension test, olfactory bulbectomy, learned helplessness, chronic mild stress, drug-withdrawal-induced anhedonia) and research strategies aimed at investigating novel targets relevant to depression in the mouse. We will focus on key questions that are considered relevant for examining the utility of such models. Further, we describe other avenues of research that may give clues as to whether indeed a genetically modified animal has alterations relevant to clinical depression. We suggest that it is prudent and most appropriate to use convergent tests that draw on different antidepressant-related endophenotypes, and complimentary physiological analyses in order to provide a program of information concerning whether a given phenotype is functionally relevant to depression-related pathology.

Animals↗
PubMed2002

[Genetically modified organisms--problems and legislation].

Genetically modified organisms are defined by law as entities capable of replication and/or transmission of hereditary material that had been altered by the insertion or removal of a DNA fragment. By the EU legal regulation as well as by the Czech law, such organisms are considered risky whereas other products of breeding, though obtained by, e.g., induced mutagenesis, are claimed as safe. Organisms transferred from other ecosystems are also considered safe. The Czech law on the use of genetically modified organisms is based on registers of users and organisms for specific use. Application for the registration that is valid as an approval should be submitted to the Ministry of Environment. The applicant is obliged to present the risk assessment of the particular use of genetically modified organisms. Genetically modified organisms are connected with certain risk to ecology, however health risks are brought about almost exclusively by microorganisms. Modified organisms used for food production are thoroughly tested for substantial equivalency with standard crops and with respect to health parameters of the protein(s) newly introduced due to genetic modification. Detail tests as well as their cost are close to the testing of new drugs. European as well as Czech rules for food labelling are motivated by the psychology of consumers rather than by health impact. They result to absurdities but do not meet the task of public psychology. This is why the EU authorities are looking for measures to change the present situation that other wise would bring Europe well behind the developed countries.

Czech Republic↗
PubMed1995

Genetically modified human epidermis overexpressing PDGF-A directs the development of a cellular and vascular connective tissue stroma when transplanted to athymic mice--implications for the use of genetically modified keratinocytes to modulate dermal regeneration.

We investigated the hypothesis that keratinocyte-produced platelet-derived growth factor-AA (PDGF-AA) is involved in epidermal-dermal interactions and that PDGF-AA is an important mediator of the temporal and spatial events of tissue repair. Retroviral-mediated gene transfer was used to introduce the gene encoding human PDGF-A into cultures of human diploid keratinocytes. Genetic modification boosted the endogenous in vitro level of PDGF-AA secretion by over 300 fold. When PDGF-secreting cells were transplanted as epithelial sheets to athymic mice, modified keratinocytes underwent terminal differentiation and generated a stratified epithelium comparable to unmodified cells. Seven days after grafting the newly synthesized connective tissue layer subjacent to the PDGF-A-modified grafts was significantly thicker, was rich in mononuclear cells and fibroblasts, and had increased numbers of blood vessels when compared to control grafts of unmodified cells. These results suggest that PDGF-AA secreted by the epidermis is an important mediator of epithelial-mesenchymal interactions and helps to promote growth and vascularization of the underlying dermal tissue. Further, these data demonstrate the feasibility of using genetically modified cells to modulate tissue regeneration.

Animals↗
PubMed2001

Enhanced matrix synthesis and in vitro formation of cartilage-like tissue by genetically modified chondrocytes expressing BMP-7.

Bone morphogenic protein-7 (BMP-7) supports ectopic cartilage and bone formation, is expressed in normal articular cartilage, and increases matrix synthesis in chondrocytes. Based on this knowledge, we hypothesized that an adenovirus (Ad) vector encoding human BMP-7 could be used to modify chondrocytes genetically to improve their capacity for cartilage repair. An adenovirus vector encoding BMP-7 (AdBMP-7) was constructed and its bioactivity confirmed by ectopic bone formation assay. AdBMP-7 modification of bovine chondrocytes induced expression of BMP-7 mRNA and bioactive protein, resulting in an increase in incorporation of 35SO4- into proteoglycan, 3H-proline uptake into protein, and the expression of the cartilage-specific matrix genes, aggrecan and type II collagen. An in vitro model of chondrocyte transplantation was used to demonstrate the feasibility of using genetically modified chondrocytes to enhance formation of cartilage-like tissue. When transplanted onto cartilage explants and maintained in vitro for 3 weeks, chondrocytes modified with AdBMP-7 formed 1.9-fold thicker tissue than chondrocytes modified with a control vector (P < 0.001). This tissue was positive for type II collagen and proteoglycan but negative for type X collagen and demonstrated a cartilage-like morphology. These observations suggest that Ad-mediated transfer of BMP-7 gene to chondrocytes enhances the chondrocyte-specific matrix synthesis and their capacity to form cartilage-like tissue, thus representing a strategy that may improve cell-based cartilage repair.

Adenoviridae↗
PubMed2002

Substantial equivalence--an appropriate paradigm for the safety assessment of genetically modified foods?

Safety assessment of genetically modified food crops is based on the concept of substantial equivalence, developed by OECD and further elaborated by FAO/WHO. The concept embraces a comparative approach to identify possible differences between the genetically modified food and its traditional comparator, which is considered to be safe. The concept is not a safety assessment in itself, it identifies hazards but does not assess them. The outcome of the comparative exercise will further guide the safety assessment, which may include (immuno)toxicological and biochemical testing. Application of the concept of substantial equivalence may encounter practical difficulties: (i) the availability of near-isogenic parental lines to compare the genetically modified food with; (ii) limited availability of methods for the detection of (un)intended effects resulting from the genetic modification; and (iii) limited information on natural variations in levels of relevant crop constituents. In order to further improve the methodology for identification of unintended effects, new 'profiling' methods are recommended. Such methods will allow for the screening of potential changes in the modified host organism at different integration levels, i.e. at the genome level, during gene expression and protein translation, and at the level of cellular metabolism.

Animals↗
PubMed1993

Correction of lysosomal storage in the liver and spleen of MPS VII mice by implantation of genetically modified skin fibroblasts.

Genetic defects of lysosomal hydrolases result in severe storage diseases and treatments based on enzyme replacement have been proposed. In mice lacking beta-glucuronidase, which develop a disease homologous to human mucopolysaccharidosis type VII (Sly syndrome), we have used autologous implants of genetically-modified skin fibroblasts for the continuous in vivo production of the enzyme. The human beta-glucuronidase cDNA was introduced with a retroviral vector into mutant mice skin fibroblasts grown in primary culture. Fourteen mutant mice were implanted intraperitoneally with these modified cells embedded into collagen lattices. All animals expressed beta-glucuronidase from the vascularized neo-organs that developed after implantation and accumulated the enzyme in their tissues. A complete disappearance of the lysosomal storage lesions was observed in their liver and spleen.

Animals↗
PubMed2005

Coral red fluorescence protein as genetic modified baculovirus tracer.

Genetic modified baculovirus (GMBV) are among the most promising alternatives to chemical insecticides. One of the deterrents to the GMBV development is the lack of simple and cost-effective methods for monitoring their efficacy and ecology in fields. Here, we demonstrate the DsRed gene from coral can serve as a convenient GMBV tracer. Insect larvae, including Trichoplusia ni, Spodoptera exigua, and Spodoptera litura, infected the GMBV containing the DsRed gene can emit red fluorescence under sun light without any prosthetic apparatus.

Animals↗
PubMed2006

Birefringent filter design by use of a modified genetic algorithm.

A modified genetic algorithm is proposed for the optimization of fiber birefringent filters. The orientation angles and the element lengths are determined by the genetic algorithm to minimize the sidelobe levels of the filters. Being different from the normal genetic algorithm, the algorithm proposed reduces the problem space of the birefringent filter design to achieve faster speed and better performance. The design of 4-, 8-, and 14-section birefringent filters with an improved sidelobe suppression ratio is realized. A 4-section birefringent filter designed with the algorithm is experimentally realized.

Journal Article↗
PubMed1993

Patents for genetically modified animals.

Should genetically engineered animals be patented? This issue has been one of the most contentious as lawmakers have grappled with how best to protect intellectual property. Since the 1980 case of Diamond v. Chakrabarty, in which the U.S. Supreme Court ruled that a living microorganism is patentable, the U.S. Patent and Trademark Office has determined that plants and nonhuman animals can be patented. These policy decisions have led to congressional debate on whether animals should be patentable subject matter. Patenting of living organisms is unique for three reasons: the invention itself is alive; the invention in some instances can reproduce itself; and the invention sometimes cannot be adequately described for patent specification purposes, leading to the need for deposit of the invention for patent purposes.

Animals↗
PubMed2006

Current and future approaches using genetically modified mice in endocrine research.

Genetically modified mouse models have been used widely to advance our knowledge in the field of endocrinology and metabolism. A number of different approaches to generate genetically modified mice are now available, which provide the power to analyze the role of individual proteins in vivo. However, there are a number of points to be considered in the use and interpretation of these models. This review discusses the advantages and disadvantages involved in the generation and use of different genetically modified mouse models in endocrine research, including conventional techniques (e.g., overexpression, knockout, and knock-in models), tissue- and/or time-specific deletion of target genes [e.g., Cre-loxP and short interfering (si)RNA transgenic approaches], and gene-trap approaches to undertake functional genomics. This review also highlights the many factors that should be considered when assessing the phenotype of these mouse models, many of which are relevant to all murine physiological studies. These approaches are a powerful means by which to dissect the function of genes and are revolutionizing our understanding of endocrine physiology and metabolism.

Animals↗
PubMed2004

Detection and traceability of genetically modified organisms in the food production chain.

Both labelling and traceability of genetically modified organisms are current issues that are considered in trade and regulation. Currently, labelling of genetically modified foods containing detectable transgenic material is required by EU legislation. A proposed package of legislation would extend this labelling to foods without any traces of transgenics. These new legislations would also impose labelling and a traceability system based on documentation throughout the food and feed manufacture system. The regulatory issues of risk analysis and labelling are currently harmonised by Codex Alimentarius. The implementation and maintenance of the regulations necessitates sampling protocols and analytical methodologies that allow for accurate determination of the content of genetically modified organisms within a food and feed sample. Current methodologies for the analysis of genetically modified organisms are focused on either one of two targets, the transgenic DNA inserted- or the novel protein(s) expressed- in a genetically modified product. For most DNA-based detection methods, the polymerase chain reaction is employed. Items that need consideration in the use of DNA-based detection methods include the specificity, sensitivity, matrix effects, internal reference DNA, availability of external reference materials, hemizygosity versus homozygosity, extrachromosomal DNA, and international harmonisation. For most protein-based methods, enzyme-linked immunosorbent assays with antibodies binding the novel protein are employed. Consideration should be given to the selection of the antigen bound by the antibody, accuracy, validation, and matrix effects. Currently, validation of detection methods for analysis of genetically modified organisms is taking place. In addition, new methodologies are developed, including the use of microarrays, mass spectrometry, and surface plasmon resonance. Challenges for GMO detection include the detection of transgenic material in materials with varying chromosome numbers. The existing and proposed regulatory EU requirements for traceability of genetically modified products fit within a broader tendency towards traceability of foods in general and, commercially, towards products that can be distinguished from each other. Traceability systems document the history of a product and may serve the purpose of both marketing and health protection. In this framework, segregation and identity preservation systems allow for the separation of genetically modified and non-modified products from "farm to fork". Implementation of these systems comes with specific technical requirements for each particular step of the food processing chain. In addition, the feasibility of traceability systems depends on a number of factors, including unique identifiers for each genetically modified product, detection methods, permissible levels of contamination, and financial costs. In conclusion, progress has been achieved in the field of sampling, detection, and traceability of genetically modified products, while some issues remain to be solved. For success, much will depend on the threshold level for adventitious contamination set by legislation.

Animals↗