Gene disruption in cells and model organisms followed by phenotypic analysis has been a traditional approach to understand gene function.
The frequent proximity of the insertions to the 5» portion of the transcription unit means that
the gene disruption in many lines could be molecularly identified by comparing the DNA sequence flanking the insertion to genomic sequence data.
In MMEJ pathway, we achieve efficient
gene disruption in human cell lines and animals by developing a computer program that assists the choice of nuclease target sites based on microhomology prediction.
While CXCR4 gene disruption remained stable over time at approximately 30 %, CXCR4
gene disruption in HIV - infected cultures increased to 87 %, 91 %, and 88 % in the presence of BK132, HxB2, and R3A respectively after 21 days of infection.
Our data demonstrate the feasibility of targeted
gene disruption in multiple rat strains within 4 months time, paving the way to a humanized monoclonal antibody platform and additional human disease models.
Not exact matches
The
disruption of prenatal cellular activity
in zebra fish, which share 80 percent of their
genes with humans and are considered a good model for studying human brain development, seemed to result
in hyperactivity, according to the Canadian study, which was published Monday
in the Proceedings of the National Academy of Sciences.
To determine if defects
in the atrial natriuretic peptide (ANP) system can cause hypertension, mice were generated with a
disruption of the proANP
gene.
«Our findings show that the
gene mutation that causes Werner syndrome results
in the disorganization of heterochromatin, and that this
disruption of normal DNA packaging is a key driver of aging,» says Juan Carlos Izpisua Belmonte, a senior author on the paper.
Disruptions to one or other of this
gene cluster leads to distinctive mutations
in which legs develop
in place of antennae, for instance, as pictured here.
Furthermore,
gene disruption by
gene editing techniques such as CRISPR - CAS resulted
in the absence of growth of parasites carrying the mutated
gene, indicating that the protein is required for parasite viability.
Even clearer evidence that
disruptions in gene imprinting can undermine mental health comes from studies of Prader - Willi syndrome, a disorder that affects growth, sexual development and cognitive ability.
Mice generated to contain a targeted
disruption of the DARPP - 32
gene showed profound deficits
in their molecular, electrophysiological, and behavioral responses to dopamine, drugs of abuse, and antipsychotic medication.
«We identified that the peculiar look of these naked lizards is due to the
disruption of the ectodysplasin - A (EDA), a
gene whose mutations
in humans and mice are known to generate substantial abnormalities
in the development of teeth, glands, nails and hairs», says Michel Milinkovitch.
The new finding is the latest evidence supporting a growing precision medicine model of psychiatric disease
in which
disruptions of certain
genes during brain development contribute to a person's risk for multiple psychiatric disorders, with other genetic or epigenetic drivers, random developmental events, or environmental influences determining the specific disease an individual develops, said senior author Benjamin Cheyette, MD, PhD, an associate professor of psychiatry and a member of the UCSF Weill Institute for Neurosciences and the Kavli Institute for Fundamental Neuroscience at UCSF.
Dr. Je and his team analysed signalling activity
in neuronal cultures that either did not have the DTNBP1
gene or had lowered levels of the
gene, because reduced DTNBP1 levels and genetic
disruptions of DTNBP1
in mice resulted
in schizophrenia - like behaviours.
«The
disruption of the circadian clock machinery seems to affect not only the rhythm of appetite regulation, but also the expression of the
genes and proteins at their absolute level,» says Turek, whose team reports its findings online today
in Science.
Over the past decade, several dozen
genes have been identified as potential culprits, and scientists believe that several
genes cause
disruptions in protein formations predisposing a person to schizophrenia.
Beverly Emanuel, a human geneticist at the University of Pennsylvania
in Philadelphia, notes that some DiGeorge patients have genetic
disruptions at the suspect region but seem to have an intact UFD1
gene.
Differences
in how
genes are controlled, or even the loss or
disruption of certain
gene regulatory elements, may explain why human ancestors evolved to be so different from their great ape relatives.
In experiments with mice, disruptions in clock genes can lead to obesity, although scientists don't yet understand the mechanis
In experiments with mice,
disruptions in clock genes can lead to obesity, although scientists don't yet understand the mechanis
in clock
genes can lead to obesity, although scientists don't yet understand the mechanism.
To begin to explore the cellular mechanisms that might be responsible for this response, histological analysis revealed less severe
disruption of spermatogenesis and
gene expression studies suggested that an interplay of ATP - binding cassette (ABC) efflux transporters and solute carrier (SLC) influx transporters
in the testicular cells might be involved.
In the R5 - ZFN control group, with intact cxcr4 genes, 88 % of CD4 + T cells expressed CXCR4 protein at day 27 post engraftment, compared to 84 % of cells in the X4 - ZFN mice (∼ 24 % cxcr4 gene disruption) as determined by a fluorescence minus - one (FMO) contro
In the R5 - ZFN control group, with intact cxcr4
genes, 88 % of CD4 + T cells expressed CXCR4 protein at day 27 post engraftment, compared to 84 % of cells
in the X4 - ZFN mice (∼ 24 % cxcr4 gene disruption) as determined by a fluorescence minus - one (FMO) contro
in the X4 - ZFN mice (∼ 24 % cxcr4
gene disruption) as determined by a fluorescence minus - one (FMO) control.
To delineate the role of Emk
in development and adult tissues, mice lacking Emk were generated by targeted
gene disruption.
After acknowledging that there can be complicated interactions between
genes, and that DNA insertion might influence regulatory networks involved
in many
genes, it also should be remembered that the original discovery of
genes was only possible because
disruption of a
gene causes a limited set of changes to the organism, such as a change
in eye colour.
A scheme of known expressed isoforms listed
in WormBase WS246 and the strategy for the
disruption of W01A8.1
gene is shown
in Figs.
Targeted
disruption of IRF - 1 or IRF - 2 results
in abnormal type I IFN
gene induction and aberrant lymphocyte development.
Disruptions in autophagy and mutations
in related
genes are linked to Parkinson's disease, type 2 diabetes and genetic diseases.
Cells rely on these pathways to respond appropriately to their environment (so that the right growth - controlling
genes get turned on
in response to a growth signal)-- but
disruptions in signaling pathways can have dire consequences.
Azoospermia
in mice with targeted
disruption of the Brek / Lmtk2 (brain - enriched kinase / lemur tyrosine kinase 2)
gene.
MEK kinase 1
gene disruption alters cell migration and c - Jun NH2 - terminal kinase regulation but does not cause a measurable defect
in NF - $ ąppa $ B activation.
The tools currently available to insert new
genes permanently into cells do so at a random site inside the cell, which occasionally results
in the
disruption of the cell's native
genes at the site of insertion, which could potentially turn the cell cancerous or cause other problems.
We remain confident that resources, such as the
gene disruption library, which integrate molecular and genetic methods will play an increasingly important role
in future biological research.
We have demonstrated that our liposomes can mediate
in vivo target mRNA delivery as well as
gene disruption using an entirely RNA - based approach.
We interfere with histone modification marks
in vivo, both genome - wide (mutant analysis) and
gene - specifically (local
disruption of chromatin structure), and analyze the effect on transcription and pluripotency.
There was a significant enrichment of
gene expression
disruption to pathways relevant
in oxidative phosphorylation; and carbohydrate, amino acid, and lipid metabolism
in diabetic co-twins.
Following up on findings from genome - wide association studies, researchers identify two mechanisms by which
disruptions in the
gene SLC16A11 may play a role
in type 2 diabetes
Scientists have for the first time shown how the
disruption of a key
gene involved
in mental illness impacts on the brain.
Insect Allies» three technical areas — trait design, insect vector optimization, and selective
gene therapy
in mature plants — layer together to support the goal of rapidly transforming mature plants to protect against agricultural
disruption without the need for extensive infrastructure.
Potential projects include identifying common pathways that modify retinal degenerative disease from a large collection of actively maintained mouse models; determining molecular networks implicated
in pathological
disruption of the retinal pigment epithelium; identifying molecular pathways that regulate postnatal ocular growth; and using mouse models to assess the pathogenic role of
gene variants that increase the risk of age - related macular degeneration as identified by human genome - wide association studies.
Overall, these observations provide a roadmap for a «human knockout project», a systematic effort to understand the phenotypic consequences of complete
disruption of
genes in humans.
If female fertility
gene disruption occurred early
in development rather than
in the germline, the same system could produce a male - linked dominant sterile - daughter effect that would be less powerful but more readily modulated (Supplementary Fig. 10).
In addition to genomic sequencing, the BDGP is 1) producing gene disruptions using P element - mediated mutagenesis on a scale unprecedented in metazoans; 2) characterizing the sequence and expression of cDNAs; and 3) developing informatics tools that support the experimental process, identify features of DNA sequence, and allow us to present up - to - date information about the annotated sequence to the research communit
In addition to genomic sequencing, the BDGP is 1) producing
gene disruptions using P element - mediated mutagenesis on a scale unprecedented
in metazoans; 2) characterizing the sequence and expression of cDNAs; and 3) developing informatics tools that support the experimental process, identify features of DNA sequence, and allow us to present up - to - date information about the annotated sequence to the research communit
in metazoans; 2) characterizing the sequence and expression of cDNAs; and 3) developing informatics tools that support the experimental process, identify features of DNA sequence, and allow us to present up - to - date information about the annotated sequence to the research community.
Bypass of senescence after
disruption of p21CIP1 / WAF1
gene in normal diploid human fibroblasts.
Mihail Sarov (Max Planck Institute, Germany): CRISPR / Cas9 - induced
disruption of
gene expression
in mouse embryonic brain
In contrast with the BN rat strain, the disruption of the Themis1 gene in LEW rats does not lead to the spontaneous development of IBD or functional Treg defect, suggesting that an epistasis phenomenon in the BN genetic background controls these phenotype
In contrast with the BN rat strain, the
disruption of the Themis1
gene in LEW rats does not lead to the spontaneous development of IBD or functional Treg defect, suggesting that an epistasis phenomenon in the BN genetic background controls these phenotype
in LEW rats does not lead to the spontaneous development of IBD or functional Treg defect, suggesting that an epistasis phenomenon
in the BN genetic background controls these phenotype
in the BN genetic background controls these phenotypes.
Disruption of the proto - oncogene int - 2
in mouse embryo - derived stem cells: A general strategy for targeting mutations to nonselectable
genes.
AAEM pointed to numerous animal studies that showed oxidative stress, altered structure and function of the liver, intestinal damage,
disruption of the immune system, increased cell growth and hundreds of alterations
in gene expressions.
This happens when there is a mutation of the FGFR3
gene (the
gene responsible for producing a protein that develops and maintains the growth of bone and brain tissue), which then causes
disruptions in skeletal development.