Browsing by Subject "Genetic engineering"

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    Analysis of the U.S. Department of Agriculture's regulation of genetically engineered crops and reproductive biology of Carex pensylvanica (Lam.)
    (2013-08) McGinnis, Esther Ebata
    This dissertation is divided into two parts. Chapters 1 through 3 are interdisciplinary and focus on legal and scientific perspectives regarding the regulation of genetically engineered crops. Chapters 4 and 5 evaluated the environmental factors that control flowering in Pennsylvania sedge (Carex pensylvanica Lam.). The commercial potential of genetically engineered (GE) crops has not been fully realized in the United States due to environmental litigation that dramatically affected the pace of GE crop development and deregulation. The USDA's Animal and Plant Health Inspection Service (APHIS) regulates GE crops. However, litigation initiated by nongovernmental organizations exposed APHIS's vulnerability to lawsuits under the National Environmental Policy Act. We concluded in chapters 1 and 2 that APHIS did not adequately evaluate the environmental risks of novel crops, and thus left itself open to litigation. In Chapter 3, we described how the biotechnology industry is attempting to avoid regulation of GE crops through the creation of a non-plant pest loophole.Pennsylvania sedge is an upland forest sedge with horticultural potential as a low maintenance groundcover. For large plantings, achenes are preferred, but Pennsylvania sedge typically produces few achenes in its native habitat. As a first step in improving achene production, Chapter 4 evaluated the effect of vernalization and photoperiod on floral initiation and development. We concluded that Pennsylvania sedge is an obligate short day plant that does not require vernalization for flowering. Plants flowered when exposed to daylengths of 6 to 12 hours. Flowering was completely inhibited with 14-hour photoperiods. Chapter 5 examined the environmental factors that control floral gender sequence and inflorescence culm heights. Plants were found to be determined and florally initiated in the fall in the northern United States. A post-floral induction chilling treatment (winter) was necessary to produce protogynous flowering and normal inflorescence culm elongation.
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    The genetically engineered minipig as a preclinical disease model for Neurofibromatosis type 1 syndrome
    (2020-09) Osum, Sara
    Neurofibromatosis type 1 (NF1) syndrome is one of the most common inherited neurological disorders, affecting about one in every three thousand individuals. The disease typically manifests in childhood and can result in significant morbidity and a shortened lifespan. Despite decades of research, there is still no cure for NF1, and treatment is largely symptomatic. This is due in part to the multisystemic nature of the disease and a lack of representative, translational animal models. Murine models of NF1 mimic individual aspects of the syndrome, but none fully represents the complexity of disease seen in human patients. There is a need for new models of NF1 to complement the mouse and improve success in clinical trials. The objective of this dissertation was to fill this need by developing and characterizing the first genetically engineered NF1+/- minipig and determining its utility as a preclinical disease model for human NF1. Using targeted gene editing and somatic cell nuclear transfer cloning, we generated NF1+/- minipigs harboring a specific human disease allele associated with severe phenotypes in NF1 patients. We enrolled cohorts of NF1+/- minipigs and wild-type litter mate controls in a longitudinal phenotyping study and assessed for manifestations of NF1 syndrome. We performed gross assessments by physical examination, radiography, and magnetic resonance imaging over time. We also assessed the histological, molecular and biochemical defects associated with NF1 using tissues and primary cells isolated from lesions in NF1+/- minipigs. We evaluated several targeted therapies currently in clinical trials for NF1-associated neoplasia using pharmacokinetic and pharmacodynamic analyses in blood and clinically relevant tissues from NF1+/- minipigs. The results of these studies show that our NF1 minipig model offers a predictive preclinical disease model that will be crucial for developing and validating new NF1-targeted therapies as well as improved imaging and surgical modalities for early detection of nervous system tumors. Furthermore, the methods presented provide a blueprint for using minipig tissues to evaluate pharmacodynamics of new targeted therapies and using primary cells from minipigs to uncover novel targets and cellular interactions within the neurofibroma microenvironment.