Microarray analyses of transgenic zebrafish expressing human KIT-D816V gene versus wild-type zebrafish
Ontology highlight
ABSTRACT:
ORGANISM(S): Danio rerio
PROVIDER: GSE54615 | GEO | 2014/02/03
SECONDARY ACCESSION(S): PRJNA237183
REPOSITORIES: GEO
Similar Datasets
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2014-02-03 | E-GEOD-54615 | biostudies-arrayexpress
Project description:Transcriptional profiling of 28 hpf zebrafish transgenic expressing human KIT-D816V mutant gene versus wild-type embryos was performed. The aim of this experiment was to determine the expression changes caused by expression of KIT-D816V oncogene. This transgenic zebrafish represents a model of systemic mastocytosis with many features of this disease present in adults, but no very clear phenotypes in embryos. Thus, we attempted to determine if there are certain expression changes, which can be used as molecular features of active KIT expressed in these embryos.
2014-02-03 | GSE54613 | GEO
Project description:Transcriptional profiling of 28 hpf zebrafish transgenic expressing human KIT-D816V mutant gene versus wild-type embryos was performed. The aim of this experiment was to determine the expression changes caused by expression of KIT-D816V oncogene. This transgenic zebrafish represents a model of systemic mastocytosis with many features of this disease present in adults, but no very clear phenotypes in embryos. Thus, we attempted to determine if there are certain expression changes, which can be used as molecular features of active KIT expressed in these embryos. Two-condition experiment, Tg(actb2:KIT-D816V) versus wild-type(AB), 4 replicate experiments with a dye-swap each time
2014-02-03 | E-GEOD-54613 | biostudies-arrayexpress
Project description:Transcriptional profiling of pooled adult kidneys from transgenic zebrafish expressing human KIT-D816V mutant gene versus wild-type zebrafish was performed. The aim of this experiment was to determine the expression and cellular changes caused by expression of KIT-D816V oncogene in the hematopoietic organ in zebrafish. This transgenic zebrafish represents a model of systemic mastocytosis with many features of this disease present in adults
2014-02-03 | GSE54614 | GEO
Project description:Transcriptional profiling of pooled adult kidneys from transgenic zebrafish expressing human KIT-D816V mutant gene versus wild-type zebrafish was performed. The aim of this experiment was to determine the expression and cellular changes caused by expression of KIT-D816V oncogene in the hematopoietic organ in zebrafish. This transgenic zebrafish represents a model of systemic mastocytosis with many features of this disease present in adults Two-condition experiment, Tg(actb2:KIT-D816V) versus wild-type(AB), one replicate of each prepared from 3 adult kidneys of each genotype and a dye-swap hybridization of these RNA samples.
2014-02-03 | E-GEOD-54614 | biostudies-arrayexpress
Project description:Acute Myeloid Leukaemia (AML) carries a 5 year survival rate of just 24%. Toxic chemotherapy regimens remain the backbone of standard of care for AML. The KIT tyrosine kinase is a recognised AML oncogene, associated with poor outcome. We recently identified DNA-PK as a novel therapeutic target in FLT3 mutant AML. The similarity between KIT and FLT3 regulated signalling pathways led us to investigate DNA-PK in KIT-mutant AML.
2023-01-26 | PXD030005 | Pride
Project description:HaHB4 is a sunflower transcription factor belonging to the homeodomain-leucine zipper I family whose ectopic expression in Arabidopsis triggers drought tolerance. The use of PCR to clone the HaHB4 coding sequence for wheat transformation caused unprogrammed mutations producing subtle differences in its activation ability in yeast. Transgenic wheat plants carrying a mutated version of HaHB4 were tested in 37 field experiments. A selected transgenic line yielded 6% more (P<0.001) and had 9.4% larger water use efficiency (P<0.02) than its control across the evaluated environments. Differences in grain yield between cultivars were explained by the 8% improvement in grain number per square meter (P<0.0001), and were more pronounced in stress (16% benefit) than in non-stress conditions (3% benefit), reaching a maximum of 97% in one of the driest environments. Increased grain number per square meter of transgenic plants was accompanied by positive trends in spikelet numbers per spike, tillers per plant, and fertile florets per plant. The gene transcripts associated with abiotic stress showed that HaHB4's action was not dependent on the response triggered either by RD19 or by DREB1a, traditional candidates related to water deficit responses. HaHB4 enabled wheat to show some of the benefits of a species highly adapted to water scarcity, especially in marginal regions characterized by frequent droughts.
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Project description:BackgroundAtypical chronic myeloid leukemia (aCML) is a rare myelodysplastic/myeloproliferative neoplasm. There is no proven standard of care treatment and the only curative option available is hematopoietic stem cell transplant. In addition to traditional chemotherapy, targeted therapy has shown to be a promising. Avapritinib is a selective type 1 tyrosine kinase inhibitor with high potency for KIT D816V and was recently approved for treatment of systemic mastocytosis. Here we present a case of aCML with novel D816V mutation treated with avapritinib for 17 months leading to clonal extinction of the driver mutation.Case presentationAn 80 year old man initially presented for evaluation of aCML. A bone marrow biopsy was completed, and next generation sequencing was notable for a novel KIT D816V mutation. Patient was started on avapritinib leading to significant improvement in leukocytosis and extinction of the D816V mutation over 17 months of treatment. The extinction was followed with serial next generation sequencing.ConclusionWe present the first case of aCML with KIT D816V driver mutation. We also demonstrate two novel management strategies. First, we show that treatment with avapritinib does not need to be limited to cases of systemic mastocytosis and could be useful in other hematologic malignancies with this driver mutation. Furthermore, with the use of serial next generation sequencing we were able to identify new emerging clones. While none of the clones noted in this study were targetable, they could be in other patients with aCML and help guide treatment.
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Project description:Currently, there are no animal models of the most common human prion disorder, sporadic Creutzfeldt-Jakob disease (CJD), in which prions are formed spontaneously from wild-type (WT) prion protein (PrP). Interestingly, bank voles (BV) exhibit an unprecedented promiscuity for diverse prion isolates, arguing that bank vole PrP (BVPrP) may be inherently prone to adopting misfolded conformations. Therefore, we constructed transgenic (Tg) mice expressing WT BVPrP. Tg(BVPrP) mice developed spontaneous CNS dysfunction between 108 and 340 d of age and recapitulated the hallmarks of prion disease, including spongiform degeneration, pronounced astrogliosis, and deposition of alternatively folded PrP in the brain. Brain homogenates of ill Tg(BVPrP) mice transmitted disease to Tg(BVPrP) mice in ?35 d, to Tg mice overexpressing mouse PrP in under 100 d, and to WT mice in ?185 d. Our studies demonstrate experimentally that WT PrP can spontaneously form infectious prions in vivo. Thus, Tg(BVPrP) mice may be useful for studying the spontaneous formation of prions, and thus may provide insight into the etiology of sporadic CJD.
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Project description:?1-Antitrypsin deficiency is an inherited condition that causes liver disease and emphysema. The normal function of this protein, which is synthesized by the liver, is to inhibit neutrophil elastase, a protease that degrades connective tissue of the lung. In the classical form of the disease, inefficient secretion of a mutant ?1-antitrypsin protein (AAT-Z) results in its accumulation within hepatocytes and reduced protease inhibitor activity, resulting in liver injury and pulmonary emphysema. Because mutant protein accumulation increases hepatocyte cell stress, we investigated whether transplanted hepatocytes expressing wild-type AAT might have a competitive advantage relative to AAT-Z-expressing hepatocytes, using transgenic mice expressing human AAT-Z. Wild-type donor hepatocytes replaced 20%-98% of mutant host hepatocytes, and repopulation was accelerated by injection of an adenovector expressing hepatocyte growth factor. Spontaneous hepatic repopulation with engrafted hepatocytes occurred in the AAT-Z-expressing mice even in the absence of severe liver injury. Donor cells replaced both globule-containing and globule-devoid cells, indicating that both types of host hepatocytes display impaired proliferation relative to wild-type hepatocytes. These results suggest that wild-type hepatocyte transplantation may be therapeutic for AAT-Z liver disease and may provide an alternative to protein replacement for treating emphysema in AAT-ZZ individuals.
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