Gene Targeting

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  Subject Areas on Research

  • A PCR-based strategy to generate integrative targeting alleles with large regions of homology. 
  • A conversation with Oliver Smithies. 
  • A family of hierarchically self-assembling linear-dendritic hybrid polymers for highly efficient targeted gene delivery. 
  • A gammaGT-AT1A receptor transgene protects renal cortical structure in AT1 receptor-deficient mice. 
  • A genetic memory initiates the epigenetic loop necessary to preserve centromere position. 
  • A mouse model of familial porphyria cutanea tarda. 
  • A new Cre driver mouse line, Tcf21/Pod1-Cre, targets metanephric mesenchyme. 
  • A new class of temporarily phenotypic enhancers identified by CRISPR/Cas9-mediated genetic screening. 
  • A suppression strategy for antibiotic discovery. 
  • AAV does the shuffle. 
  • ATM Paradoxically Promotes Oncogenic Transformation via Transcriptional Reprogramming. 
  • Absence of the CAAX endoprotease Rce1: effects on cell growth and transformation. 
  • Adeno-associated virus-mediated ILK gene silencing in the rat NAc core. 
  • Adenosine-deaminase-deficient mice die perinatally and exhibit liver-cell degeneration, atelectasis and small intestinal cell death. 
  • Advanced magnetic resonance imaging of cerebral cavernous malformations: part II. Imaging of lesions in murine models. 
  • Advances in targeted genome editing. 
  • An analysis of T cell intrinsic roles of E2A by conditional gene disruption in the thymus. 
  • An essential role for an inositol polyphosphate multikinase, Ipk2, in mouse embryogenesis and second messenger production. 
  • Angiotensin-converting enzyme 2 gene targeting studies in mice: mixed messages. 
  • Anti-gene padlocks eliminate Escherichia coli based on their genotype. 
  • Assessing a role for enhancer-blocking activity in gene regulation within the murine T-cell receptor alpha/delta locus. 
  • B-lymphocyte development is regulated by the combined dosage of three basic helix-loop-helix genes, E2A, E2-2, and HEB. 
  • Behavioral characterization of P311 knockout mice. 
  • Bmp4 is required for the generation of primordial germ cells in the mouse embryo. 
  • Bone morphogenetic protein 8A plays a role in the maintenance of spermatogenesis and the integrity of the epididymis. 
  • Bone morphogenetic protein-4 is required for mesoderm formation and patterning in the mouse. 
  • CD22 negatively and positively regulates signal transduction through the B lymphocyte antigen receptor. 
  • Cas9 loosens its grip on off-target sites. 
  • Cell type-specific delivery of siRNAs with aptamer-siRNA chimeras. 
  • Complexity of CNC transcription factors as revealed by gene targeting of the Nrf3 locus. 
  • Conditional knockout of Fgf13 in murine hearts increases arrhythmia susceptibility and reveals novel ion channel modulatory roles. 
  • Defective T cell development and function in the absence of Abelson kinases. 
  • Deletion of the glutamate carboxypeptidase II gene in mice reveals a second enzyme activity that hydrolyzes N-acetylaspartylglutamate. 
  • Delivery of viral vectors to tumor cells: extracellular transport, systemic distribution, and strategies for improvement. 
  • Design, Assembly, and Characterization of TALE-Based Transcriptional Activators and Repressors. 
  • Disruption of Mekk2 in mice reveals an unexpected role for MEKK2 in modulating T-cell receptor signal transduction. 
  • Disruption of the mouse oestrogen receptor gene: resulting phenotypes and experimental findings. 
  • Disruption of the uncoupling protein-2 gene in mice reveals a role in immunity and reactive oxygen species production. 
  • Dopaminergic supersensitivity in G protein-coupled receptor kinase 6-deficient mice. 
  • Dramatically different phenotypes in mouse models of human Tay-Sachs and Sandhoff diseases. 
  • Effects on blood pressure and exploratory behaviour of mice lacking angiotensin II type-2 receptor. 
  • Energy metabolism in uncoupling protein 3 gene knockout mice. 
  • Enhanced contractility and decreased beta-adrenergic receptor kinase-1 in mice lacking endogenous norepinephrine and epinephrine. 
  • Enhanced pancreatic cancer gene therapy by combination of adenoviral vector expressing c-erb-B2 (Her-2/neu)-targeted immunotoxin with a replication-competent adenovirus or etoposide. 
  • Estrogen receptor gene disruption: molecular characterization and experimental and clinical phenotypes. 
  • Examination of Endogenous Rotund Expression and Function in Developing Drosophila Olfactory System Using CRISPR-Cas9-Mediated Protein Tagging. 
  • Exploring type I angiotensin (AT1) receptor functions through gene targeting. 
  • Expression of a beta-adrenergic receptor kinase 1 inhibitor prevents the development of myocardial failure in gene-targeted mice. 
  • Expression of the 71 kDa dystrophin isoform (Dp71) evaluated by gene targeting. 
  • Functional characterization of the S. cerevisiae genome by gene deletion and parallel analysis. 
  • Gene Function Analysis in the Ubiquitous Human Commensal and Pathogen Malassezia Genus. 
  • Gene delivery through cell culture substrate adsorbed DNA complexes. 
  • Gene targeting to the ROSA26 locus directed by engineered zinc finger nucleases. 
  • Gene targeting: applications in transplantation research. 
  • Gene therapy for prostate cancer: where are we now? 
  • Gene-targeting studies of the renin-angiotensin system: mechanisms of hypertension and cardiovascular disease. 
  • Generation and characterization of mice lacking gastrin-releasing peptide receptor. 
  • Generation of a Magoh conditional allele in mice. 
  • Generation of primary tumors with Flp recombinase in FRT-flanked p53 mice. 
  • Genetic ablation of phosphatidylinositol transfer protein function in murine embryonic stem cells. 
  • Genetic deletion of receptor for hyaluronan-mediated motility (Rhamm) attenuates the formation of aggressive fibromatosis (desmoid tumor). 
  • Genetic targeting for cardiovascular therapeutics: are we near the summit or just beginning the climb? 
  • Genetic therapies for cardiovascular diseases. 
  • Genetic variation in SP-A2 leads to differential binding to Mycoplasma pneumoniae membranes and regulation of host responses. 
  • Genome-editing Technologies for Gene and Cell Therapy. 
  • Group II introns designed to insert into therapeutically relevant DNA target sites in human cells. 
  • Heme oxygenase 1 is required for mammalian iron reutilization. 
  • Heme oxygenase-1 gene ablation or expression modulates cisplatin-induced renal tubular apoptosis. 
  • High incidence of T-cell tumors in E2A-null mice and E2A/Id1 double-knockout mice. 
  • Hippocampal long-term potentiation is normal in heme oxygenase-2 mutant mice. 
  • Human apoE targeted replacement mouse lines: h-apoE4 and h-apoE3 mice differ on spatial memory performance and avoidance behavior. 
  • Human apoE4-targeted replacement mice display synaptic deficits in the absence of neuropathology. 
  • Human apolipoprotein E4 targeted replacement mice show increased prevalence of intracerebral hemorrhage associated with vascular amyloid deposition. 
  • Hyperlocomotion and indifference to cocaine and amphetamine in mice lacking the dopamine transporter. 
  • Hypertension and impaired glycine handling in mice lacking the orphan transporter XT2. 
  • Hypertrophic cardiomyopathy in cardiac myosin binding protein-C knockout mice. 
  • IFN-gamma induction of p21(WAF1) is required for cell cycle inhibition and suppression of apoptosis. 
  • Identification of specific EP receptors responsible for the hemodynamic effects of PGE2. 
  • In vivo reprogramming of hTERT by trans-splicing ribozyme to target tumor cells. 
  • Inhibition of adult neurogenesis by inducible and targeted deletion of ERK5 mitogen-activated protein kinase specifically in adult neurogenic regions impairs contextual fear extinction and remote fear memory. 
  • Inhibition of neuronal maturation in primary hippocampal neurons from tau deficient mice. 
  • Insights into the functions of type 1 (AT1) angiotensin II receptors provided by gene targeting. 
  • Interacting targets of the farnesyl of transducin gamma-subunit. 
  • Jumping at the chance for precise DNA integration. 
  • Kctd13-deficient mice display short-term memory impairment and sex-dependent genetic interactions. 
  • LKLF: A transcriptional regulator of single-positive T cell quiescence and survival. 
  • Leukocyte migration is regulated by L-selectin endoproteolytic release. 
  • Liver-specific loss of long chain acyl-CoA synthetase-1 decreases triacylglycerol synthesis and beta-oxidation and alters phospholipid fatty acid composition. 
  • Loss-of-function genomic variants highlight potential therapeutic targets for cardiovascular disease. 
  • Low-Dose Irradiation Enhances Gene Targeting in Human Pluripotent Stem Cells. 
  • Lymphocyte homing and leukocyte rolling and migration are impaired in L-selectin-deficient mice. 
  • Mammalian Sir2 homolog SIRT3 regulates global mitochondrial lysine acetylation. 
  • Meeting report: targeting protein phosphatases-medicines for the new millenium. 
  • Mending the message. 
  • MicroRNAs preferentially target the genes with high transcriptional regulation complexity. 
  • Minimal phenotype of mice homozygous for a null mutation in the forkhead/winged helix gene, Mf2. 
  • Molecular determinants of synapsin targeting to presynaptic terminals. 
  • Mutations in INVS encoding inversin cause nephronophthisis type 2, linking renal cystic disease to the function of primary cilia and left-right axis determination. 
  • Optimizing Nervous System-Specific Gene Targeting with Cre Driver Lines: Prevalence of Germline Recombination and Influencing Factors. 
  • Physiological impact of increased expression of the AT1 angiotensin receptor. 
  • Positional cloning uncovers mutations in PLCE1 responsible for a nephrotic syndrome variant that may be reversible. 
  • Prostate cancer gene therapy. 
  • Reading frame correction by targeted genome editing restores dystrophin expression in cells from Duchenne muscular dystrophy patients. 
  • Regional-specific effects of ovarian hormone loss on synaptic plasticity in adult human APOE targeted replacement mice. 
  • Regulation of E2A gene expression in B-lymphocyte development. 
  • Regulation of blood pressure by the type 1A angiotensin II receptor gene. 
  • Requirement of MIP-1 alpha for an inflammatory response to viral infection. 
  • Retrograde gene delivery to hypoglossal motoneurons using adeno-associated virus serotype 9. 
  • Reverse engineering gene regulatory networks. 
  • Role of alternative oxidase gene in pathogenesis of Cryptococcus neoformans. 
  • Role of mouse cryptochrome blue-light photoreceptor in circadian photoresponses. 
  • SCAR, a WASP-related protein, isolated as a suppressor of receptor defects in late Dictyostelium development. 
  • SR1, a mouse odorant receptor with an unusually broad response profile. 
  • Separating the wheat from the chaff: focus on "in silico data filtering to identify new angiogenesis targets from a large in vitro gene profile data set". 
  • SpHnf6, a transcription factor that executes multiple functions in sea urchin embryogenesis. 
  • Specific targeting of gene expression to a subset of human trabecular meshwork cells using the chitinase 3-like 1 promoter. 
  • Specification of Vδ and Vα usage by Tcra/Tcrd locus V gene segment promoters. 
  • Structure-guided reprogramming of serine recombinase DNA sequence specificity. 
  • Suppression of hepatitis B virus DNA accumulation in chronically infected cells using a bacterial CRISPR/Cas RNA-guided DNA endonuclease. 
  • Synergistic enhancement of both initiation and elongation by acidic transcription activation domains. 
  • Synthesis of programmable integrases. 
  • Targeted disruption of the leukotriene B(4) receptor in mice reveals its role in inflammation and platelet-activating factor-induced anaphylaxis. 
  • Targeted downregulation of N-acetylgalactosamine 4-sulfate 6-O-sulfotransferase significantly mitigates chondroitin sulfate proteoglycan-mediated inhibition. 
  • Targeted entry via somatostatin receptors using a novel modified retrovirus glycoprotein that delivers genes at levels comparable to those of wild-type viral glycoproteins. 
  • Targeted gene deletion of heme oxygenase 2 reveals neural role for carbon monoxide. 
  • Targeted gene transfer to Schlemm's canal by retroperfusion. 
  • Targeted inactivation of synaptic HRG4 (UNC119) causes dysfunction in the distal photoreceptor and slow retinal degeneration, revealing a new function. 
  • Targeted metabolomics and mathematical modeling demonstrate that vitamin B-6 restriction alters one-carbon metabolism in cultured HepG2 cells. 
  • Targeted plasmid integration into the human genome by an engineered zinc-finger recombinase. 
  • Targeted suppression of beta-catenin blocks intestinal adenoma formation in APC Min mice. 
  • Targeting genes in the renin-angiotensin system. 
  • Targeting the receptor-Gq interface to inhibit in vivo pressure overload myocardial hypertrophy. 
  • Tea with Dr Oliver Smithies, 2007 Nobel laureate in physiology and medicine. Interview by Dr. Anthony Viera. 
  • The Development of TALE Nucleases for Biotechnology. 
  • The Role of Pancreatic Preproglucagon in Glucose Homeostasis in Mice. 
  • The colorectal microRNAome. 
  • The combined functions of proapoptotic Bcl-2 family members bak and bax are essential for normal development of multiple tissues. 
  • The gene encoding bone morphogenetic protein 8B is required for the initiation and maintenance of spermatogenesis in the mouse. 
  • The menthol receptor TRPM8 is the principal detector of environmental cold. 
  • The role of apolipoprotein E in Alzheimer's disease: pharmacogenomic target selection. 
  • Tissue-specific inactivation of murine M6P/IGF2R. 
  • Transcription factor Nrg1 mediates capsule formation, stress response, and pathogenesis in Cryptococcus neoformans. 
  • Transgenic targeting of a dominant negative corepressor to liver and analyses by cDNA microarray. 
  • Trex2 enables spontaneous sister chromatid exchanges without facilitating DNA double-strand break repair. 
  • Type III hyperlipoproteinemia and spontaneous atherosclerosis in mice resulting from gene replacement of mouse Apoe with human Apoe*2. 
  • VEGF inhibition and renal thrombotic microangiopathy. 
  • Windows into development: historic, current, and future perspectives on transgenic zebrafish. 
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  Keywords of People

  • Hartemink, Alexander J., Professor in the Department of Computer Science, Biology
  • Hirschey, Matthew, Associate Professor of Medicine, Pharmacology & Cancer Biology
  • Hogan, Brigid L. M., George Barth Geller Distinguished Professor for Research in Molecular Biology, Cell Biology
  • Krangel, Michael S., George Barth Geller Distinguished Professor of Immunology, Immunology
  • Liton, Paloma Borrajo, Associate Professor in Ophthalmology, Pathology
  • Silver, Debra Lynn, Associate Professor of Molecular Genetics and Microbiology, Duke Science & Society
  • Sunday, Mary Elizabeth Anne, Professor of Pathology, Cell Biology
  • Taylor, Gregory Alan, Professor in Medicine, Immunology
  • Zhong, Xiaoping, Professor of Pediatrics, Immunology