A5022020811- RNA modifications and cancer
- RNA Research and Splicing
- Cystic Fibrosis Research Advances
- Congenital heart defects research
- Cancer-related gene regulation
- Energy Harvesting in Wireless Networks
- CRISPR and Genetic Engineering
- Animal Genetics and Reproduction
- Digestive system and related health
- Developmental Biology and Gene Regulation
- Cancer-related molecular mechanisms research
- Neonatal Respiratory Health Research
- Blood Coagulation and Thrombosis Mechanisms
- Congenital gastrointestinal and neural anomalies
- RNA regulation and disease
- Platelet Disorders and Treatments
- Genomics and Chromatin Dynamics
- Cellular transport and secretion
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Congenital Ear and Nasal Anomalies
- Treatment of Major Depression
- Celiac Disease Research and Management
- Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Workplace Health and Well-being
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
University School
1992-2024
Case Western Reserve University
1993-2024
Target (United States)
2023-2024
Université de Sherbrooke
1993-2016
Hôpital Necker-Enfants Malades
2009
Inserm
2009
University Hospitals of Cleveland
2000-2001
Mount Sinai Hospital
2000
Lunenfeld-Tanenbaum Research Institute
2000
Fox Chase Cancer Center
1994
In vivo genome correction holds promise for generating durable disease cures; yet, effective stem cell editing remains challenging. this work, we demonstrate that optimized lung-targeting lipid nanoparticles (LNPs) enable high levels of in cells, yielding responses. Intravenously administered gene-editing LNPs activatable tdTomato mice achieved >70% lung editing, sustaining expression >80% epithelial cells 660 days. Addressing cystic fibrosis (CF), NG-ABE8e messenger RNA (mRNA)-sgR553X...
Cajal bodies (CBs) are nuclear suborganelles involved in the biogenesis of small ribonucleoproteins (snRNPs). In addition to snRNPs, they highly enriched basal transcription and cell cycle factors, nucleolar proteins fibrillarin (Fb) Nopp140 (Nopp), survival motor neuron (SMN) protein complex, CB marker protein, p80 coilin. We report generation knockout mice lacking COOH-terminal 487 amino acids Northern Western blot analyses demonstrate that we have successfully removed full-length coilin...
The rapid, transient induction of the c-fos proto-oncogene by serum growth factors is mediated response element (SRE). SRE shares homology with muscle regulatory (MRE) skeletal alpha-actin promoter. It not known how these elements respond to proliferative and cell-type-specific signals, but appears involve binding factor (SRF) other proteins. Here, we report that YY1, a multifunctional transcription factor, binds MRE sequences in vitro. methylation interference footprint YY1 overlaps SRF,...
Adult vascular smooth muscle cells dedifferentiate and reenter the cell cycle in response to growth factor stimulation. Here we describe molecular cloning from muscle, structure, chromosomal location of a diverged homeobox gene, Gax, whose expression is largely confined cardiovascular tissues adult. In quiescent adult rat cells, Gax mRNA levels are down-regulated as much 15-fold within 2 h when these induced proliferate with platelet-derived (PDGF) or serum factors. This reduction transient,...
The metabolic function of PEPCK-C is not fully understood; deletion the gene for enzyme in mice provides an opportunity to assess its function.The cytosolic form phosphoenolpyruvate carboxykinase (GTP) (EC 4.1.1.32) (PEPCK-C) was deleted by homologous recombination (PEPCK-C-/- mice) and consequences assessed.PEPCK-C-/- became severely hypoglycemic day two after birth then died with profound hypoglycemia (12 mg/dl). had milk their stomachs at administration glucose raised concentration blood...
Nonsense mutations are present in 10% of patients with CF, produce a premature termination codon CFTR mRNA causing early translation, and lead to lack function. There no currently available animal models which contain nonsense mutation the endogenous Cftr locus that can be utilized test therapies. In this study, we create CF mouse model carrying G542X using CRISPR/Cas9 gene editing. The has reduced levels, demonstrates absence function, displays characteristic manifestations mice such as...
BackgroundProtease-activated receptor 4 (PAR4) mediates thrombin signaling on platelets and other cells. Our recent structural studies demonstrated that a single nucleotide polymorphism in extracellular loop 3 PAR4-P310L (rs2227376) leads to hyporeactive receptor.ObjectivesThe goal of this study was determine how the PAR4 variant impacts platelet function vivo using novel knock-in mouse model (PAR4-322L).MethodsA point mutation introduced into gene F2rl3 via CRISPR/Cas9 create PAR4-P322L,...
The rapid, transient induction of the c-fos proto-oncogene by serum growth factors is mediated response element (SRE). SRE shares homology with muscle regulatory (MRE) skeletal alpha-actin promoter. It not known how these elements respond to proliferative and cell-type-specific signals, but appears involve binding factor (SRF) other proteins. Here, we report that YY1, a multifunctional transcription factor, binds MRE sequences in vitro. methylation interference footprint YY1 overlaps SRF,...
We report here the cloning of a cDNA encoding homeobox transcription factor from vascular smooth muscle and describe its unique pattern mRNA expression at different stages in development. The isolated is 1576 base pairs length not including poly(A) tail contains an open reading frame coding for predicted 372-amino acid protein. During early embryogenesis, was detected neural tube with sharp boundary occurring anterior position, myelencephalon, third fourth branchial arches, vessels leading...
Abstract The intestinal epithelial barrier is critical to limit potential harmful consequences from exposure deleterious luminal contents on the organism. Although this functionally important along entire gut, specific regional regulatory mechanisms involved in maintenance of are poorly defined. Herein, we identified Gata4 as a crucial regulator integrity mouse proximal epithelium. Conditional deletion intestine led drastic increase claudin-2 expression that was associated with an gut...
Diseases with a genetic basis can be modeled knockout, knock-in, and conditional mutant gene-targeted mice. In the following, we provide detailed protocols for gene targeting. Gene targeting of embryonic stem cells accomplished by laboratories equipped tissue culture. Alternatively, many gene-targeting services divide work customer lab. this collaborative situation, knowledge entire process helps ensure successful outcome. The construction chimeras germ-line transmission is not described...
Abstract Rhodopsin mislocalization encompasses various blind conditions. is the primary factor leading to rod photoreceptor dysfunction and degeneration in autosomal dominant retinitis pigmentosa (adRP) caused by class I mutations. In this study, we report a new knock‐in mouse model that harbors Q344X mutation endogenous rhodopsin gene, which causes an pattern. Rho Q344X/+ mice, mRNA transcripts from wild‐type ( ) mutant alleles are expressed at equal levels. However, amount of RHO protein...
Adult vascular smooth muscle cells dedifferentiate and reenter the cell cycle in response to growth factor stimulation. Here we describe molecular cloning from muscle, structure, chromosomal location of a diverged homeobox gene, Gax, whose expression is largely confined cardiovascular tissues adult. In quiescent adult rat cells, Gax mRNA levels are down-regulated as much 15-fold within 2 h when these induced proliferate with platelet-derived (PDGF) or serum factors. This reduction transient,...
Nested chromosomal deletions are powerful genetic tools. They particularly suited for identifying essential genes in development either directly or by screening induced mutations against a deletion. To apply this approach to the functional analysis of mouse chromosome 2, strategy rapid generation nested with Cre recombinase was developed and tested. A loxP site targeted Notch1 gene on 2. line cotransfected second plasmid transient expression Cre. Independent random integrations onto direct...
Abstract Background Protease activated receptor 4 (PAR4) mediates thrombin signaling on platelets and other cells. Our recent structural studies demonstrated a single nucleotide polymorphism in extracellular loop 3 (ECL3), PAR4-P310L (rs2227376) leads to hypo-reactive receptor. Objectives The goal of this study was determine how the PAR4 variant ECL3 impacts platelet function vivo using novel knock-in mouse model (PAR4-322L). Methods A point mutation introduced into gene, F2rl3, via...
People with cystic fibrosis carrying two nonsense alleles lack CFTR-specific treatment. Growing evidence supports the hypothesis that mutation identity affects therapeutic response, calling for mutation-specific CF models. We describe a novel W1282X mouse model and compare it to an existing G542X mouse.
Mutations in proteolipid protein 1 ( PLP1 ) result failure of myelination and severe neurological dysfunction the X-linked pediatric leukodystrophy Pelizaeus-Merzbacher disease (PMD). The majority variants, including supernumerary copies various point mutations, lead to early mortality. However, -null patients mice display comparatively mild phenotypes, suggesting that reduction aberrant expression might provide a therapeutic strategy across PMD genotypes. Here we show, CRISPR-Cas9 mediated...