Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA118547 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Choroideremia (CHM) is a progressive X-linked retinopathy caused by mutations in the CHM gene, which encodes Rab escort protein-1 (REP-1), an escort protein involved in the prenylation of Rabs. Under-prenylation of certain Rabs, as a result of loss of function mutations in REP-1, could affect vesicular trafficking, exocytosis and secretion. To evaluate this hypothesis, intracellular vesicle transport, lysosomal acidification and rates of proteolytic degradation were studied in monocytes (CD14+ fraction) and primary skin fibroblasts from the nine age-matched controls and thirteen CHM patients carrying 10 different loss-of-function mutations. expression data were collected from 6 CHM patients' monocytes and 4 CHM primary fibroblasts cultures, monocytes or FB from 5 normal age-matched subjects were used as a control
2010-02-21 | E-GEOD-17549 | biostudies-arrayexpress
Project description:Choroideremia (CHM) is a progressive X-linked retinopathy caused by mutations in the CHM gene, which encodes Rab escort protein-1 (REP-1), an escort protein involved in the prenylation of Rabs. Under-prenylation of certain Rabs, as a result of loss of function mutations in REP-1, could affect vesicular trafficking, exocytosis and secretion. To evaluate this hypothesis, intracellular vesicle transport, lysosomal acidification and rates of proteolytic degradation were studied in monocytes (CD14+ fraction) and primary skin fibroblasts from the nine age-matched controls and thirteen CHM patients carrying 10 different loss-of-function mutations.
2010-01-27 | GSE17549 | GEO
Project description:Recombinant adeno-associated viruses (rAAVs) are the predominant gene therapy vector. Several rAAV vectored therapies have achieved regulatory approval, but production of sufficient rAAV quantities remains difficult. The AAV Rep proteins, which are essential for genome replication and packaging, represent a promising engineering target for improvement of rAAV production but remain underexplored. To gain a comprehensive understanding of the Rep proteins and their mutational landscape, we assayed the effects of all 39,297 possible single codon mutations to the AAV2 rep gene on AAV2 production. Most beneficial variants are not observed in nature, indicating that improved production may require synthetic mutations. Additionally, the effects of AAV2 rep mutations were largely consistent across capsid serotypes, suggesting that production benefits are capsid independent. Our results provide a detailed sequence-to-function map that enhances our understanding of Rep protein function and lays the groundwork for Rep engineering and enhancement of large scale gene therapy production.
2023-02-28 | GSE226265 | GEO
Project description:To determine what genes are affect to the reduction in mutation frequency by 500 µGy gamma irradiation of Drosophila melanogaster. The strain is w[1118] (a loss of function mutant of compound eye pigment gene white with Canton-S background). Experiment Overall Design: 15 samples are analyzed. The control and four time course (5, 30, 60 and 90min), 3 Biological rep. (A to C).
2008-03-13 | E-GEOD-9552 | biostudies-arrayexpress
Project description:Normal neural development is essential for the formation of neuronal networks and brain function. cTAGE5/MEA6 plays a critical role in the secretion of proteins. However, its roles in the transport of non-secretory cellular components and in brain development remain unknown. Here, we show that cTAGE5/MEA6 is essential for brain development and function. Conditional knockout of cTAGE5/MEA6 in the brain leads to severe defects in neural development, including deficits in dendrite outgrowth and branching, synapse formation and/or maintenance, astrocyte activation, and abnormal behaviors. We reveal that loss of cTAGE5/MEA6 affects the interaction between the coat protein complex II (COPII) components, SAR1 and SEC23, leading to persistent activation of SAR1 and defects in COPII vesicle formation and transport from the ER to Golgi, as well as disturbed trafficking of membrane components in neurons. These defects affect not only the transport of materials required for the development of dendrites and spines, but also the signaling pathways required for neuronal development. Since mutations in cTAGE5/MEA6 have been found in patients with Fahr’s disease, our study potentially also provides insight into the pathogenesis of this disorder.
2018-09-18 | PXD010386 | Pride
Project description:Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a fatal brain disorder featuring cerebellar neurodegeneration leading to spasticity and ataxia. ARSACS is caused by mutations in the SACS gene that encodes sacsin, a massive 4579 amino acid protein with multiple modular domains. Here we demonstrate that sacsin binds to microtubules and regulates microtubule dynamics. Loss of sacsin function in knockout cell lines, knockdown and knockout neurons, and patient fibroblasts leads to alterations in lysosomal transport, positioning, function and reformation following autophagy.
2022-10-15 | PXD033823 | Pride
Project description:Affect of Socs2 loss-of-function on liver regeneration
| PRJNA225288 | ENA
Project description:Transcriptome study of MYBPC3 loss of function mutations
| PRJNA591586 | ENA
Project description:Eye formation is regulated by a complex network of eye field transcription factors (EFTFs), including LIM-homeodomain gene LHX2. We disrupted LHX2 function at different stages during this process using a conditional knock-out strategy in mice. We find that LHX2 function is required in an ongoing fashion to maintain optic identity across multiple stages, from the formation of the optic vesicle to the differentiation of the neuroretina. At each stage, loss of Lhx2 led to upregulation of a set of molecular markers that are normally expressed in the thalamic eminence and in the anterodorsal hypothalamus in a portion of the optic vesicle or retina. Furthermore, the longer LHX2 function was maintained, the further optic morphogenesis progressed. Early loss of function caused profound mispatterning of the entire telencephalic-optic-hypothalamic field, such that the optic vesicle became mispositioned and appeared to arise from the diencephalic-telencephalic boundary. At subsequent stages, loss of Lhx2 did not affect optic vesicle position but caused arrest of optic cup formation. If Lhx2 was selectively disrupted in the neuroretina from E11.5, the neuroretina showed gross dysmorphology along with aberrant expression of markers specific to the thalamic eminence and anterodorsal hypothalamus. Our findings indicate a continual requirement for LHX2 throughout the early stages of optic development, not only to maintain optic identity by suppressing alternative fates but also to mediate multiple steps of optic morphogenesis. These findings provide new insight into the anophthalmic phenotype of the Lhx2 mutant and reveal novel roles for this transcription factor in eye development.
2017-09-08 | GSE87707 | GEO
Project description:Muscle tissue was longitudinally characterized histologically for electron transport function by staining 1mm of quadriceps muscle at 70 micron intervals for the activities of two complexes in the mitochondrial electron transport chain, Cytochrome C Oxidase and Succinate Dehydrogenase. Unstained serial cryosections were prepared for Laser Capture Microdissection. Target cells from the serial sections were isolated and pooled for RNA extraction, amplification and hybridization on Affymetrix microarrays. We selected homogeneous populations of muscle fibers for expression profiling based upon the presence/absence of electron transport dysfunction caused by the somatic accumulation of mitochondrial DNA deletion mutations. The design of this experiment is limited by the source tissue which is individually identified cells harboring intracellular clonal expansions of mitochondrial DNA deletion mutations. These unique and rare cells were identified in rat Vastus lateralis tissue in an aged 36-month old F344xBN F1 hybrid rat by exhaustive serial sectioning and subsequent histological characterization. Unstained serial sections where isolated by LCM and the purified RNA was amplified by 2 rounds of RNA based transcription prior to fragmentation and hybridization on rat genome affymetrix chips. Two populations of cells were analyzed, Electron transport deficient and normal control cells from the same animal.
2013-03-01 | E-GEOD-35607 | biostudies-arrayexpress