2 edition of Studies of the notch signaling pathway using transgenic mouse models found in the catalog.
Studies of the notch signaling pathway using transgenic mouse models
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The Notch signaling pathway is a cell communication pathway essential for formation of multiple systems during mammalian development. Aberrant Notch signaling is associated with a variety of human diseases. Functional studies of Notch in mice have been limited because both the absence and overexpression of Notch results in embryonic lethality. To investigate the effects of Notch signaling in vivo, three lines of Notch transgenic mice have been created that have a floxed beta-geo/stop signal between a strong promoter and the constitutively active intracellular domain of Nothch1 (IC-Notch1). IC-Notch1 can be activated after the introduction of Cre recombinase and its expression is detected through a co-expressed EGFP or hPLAP. Double transgenic IC-Notch1/pCX-Cre embryos in which IC-Notch1 expression was globally activated died at E9.5 with lack of neural tube closure, disrupted vasculature and irregular somites, demonstrating that expression of IC-Notch1 can be effectively activated by Cre recombinase. Endothelial/hematopoietic specific expression of IC-Notch1 in double transgenic IC-Notch1/Tie2-Cre embryos induced embryonic lethality at E9.5 with defects in vascular development, but did not affect primitive hematopoiesis. The Snail repressor, a mediator of endothelial-to-mesenchymal transition, was upregulated by IC-Notch1 expression in embryonic heart.To avoid the embryonic lethality, inducible IC-Notch1 expression in adult mice was achieved by crossing IC-Notch1 mice with a Cre transgene under the tetracycline operator controlled Cre (tet-O-Cre) and tetracycline transactivator under the control of Tie2 promoter (Tie2-tTA). Using this system, IC-Notch1/tet-O-Cre/Tie2-tTA mice survived embryonic development when maintained on tetracycline. After withdrawing tetracycline post-natally, expression of IC-Notch1 was detected in endothelial and hematopoietic cells by immunostaining of the GFP reporter. The IC-Notch1 expressing females were less fertile with lack of mature follicles. Matrigel plug assay showed that IC-Notch1 expression in adult mice inhibited bFGF-induced, but not VEGF induced neovascularization. In addition, 50% of transgenic mice with IC-Notch1 expression developed enlarged hematopoietic organs. Immunohistochemistry showed extensive T cell infiltration in various organs. Thus, constitutive active Notch signaling inhibited angiogenesis and induced T cell hyperproliferation in adults. This study provided a series of mouse models and valuable insights to design therapies for vessel related diseases and T cell lymphoma.
|Statement||by Ju Liu.|
|The Physical Object|
|Pagination||xiv, 189 leaves.|
|Number of Pages||189|
Dickkopf 3 (Dkk3) is a modulator of the Wnt signaling pathway and is physiologically expressed in the brain. The role of Dkk3 in the pathogenesis of AD has not been evaluated. In the present study, we determined that Dkk3 expression was significantly decreased in brain tissue from AD patients and the AD transgenic mouse model APPswe/PS1dE9 (AD Cited by: 2. A major function of the TRIF-dependent TLR signaling pathway is to mediate the induction of Type I IFNs and IFN-inducible genes. 34 This pathway involves recruitment of Cited by:
Author summary Some deleterious gene mutations only affect a subset of genetically mutant animals. This widespread phenomenon, known as mutant incomplete penetrance, complicates discovery of causative gene mutations in both model organisms and human disease. This study utilized the zebrafish mef2ca transcription factor mutant that produces craniofacial skeleton defects with incomplete Cited by: 1. The Crk adaptor proteins (Crk and CrkL) constitute an integral part of a network of essential signal transduction pathways in humans and other organisms that act as major convergence points in tyrosine kinase signaling. Crk proteins integrate signals from a wide variety of sources, including growth factors, extracellular matrix molecules, bacterial pathogens, and apoptotic by:
Murine NOTCH1 leukemias lacking Pten remain dependent on Notch signaling and are GSI sensitive. (A) Proliferation and (B) cell size analysis of primary mouse LP-ΔPEST leukemias on wild-type (WT) and Pten/Ink4a/Arf-null backgrounds treated with γ-secretase inhibitor (GSI) to block Notch by: Catenin beta-1, also known as β-catenin, is a protein that in humans is encoded by the CTNNB1 gene.. β-catenin is a dual function protein, involved in regulation and coordination of cell–cell adhesion and gene humans, the CTNNB1 protein is encoded by the CTNNB1 gene. In Drosophila, the homologous protein is called armadillo. β-catenin is a subunit of the cadherin protein Aliases: CTNNB1, CTNNB, MRD19, armadillo, .
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The role of Notch signaling in bone homeostasis with either cell culture or mouse model. Stimulatory and inhibitory e ﬀ ects of Notch signaling pathway on osteogenesis were both reported [. Since, the PI3K–Akt signaling pathway is activated in many tumors, PTEN is considered as an antitumoral protein.
Over the years, several authors attempted to link Notch and AKT. As we already developed in a previous section, Notch1 conveys the most prominent genetic T-ALL. Notch signaling pathway.
Notch receptors and ligands are expressed in the developing pancreas starting from E in the mouse pancreatic epithelium, with the exception of Notch 3 and Notch 4, which are in mesenchymal and endothelial cells, respectively (Lammert, Brown, & Melton, ). Human and mouse genetic studies have demonstrated myriad mutations in the Notch signaling pathway that causes skeletal defects [19,20].
Previous studies showed conflicting results on the role of Notch signaling in bone homeostasis with either cell culture or mouse : Sung-Tzu Liang, Jung-Ren Chen, Jhih-Jie Tsai, Yu-Heng Lai, Chung-Der Hsiao.
The analysis of genetically modified mouse models has been particularly important to understand the role of individual genes (Scheid et al., ). The first event in the normal wound repair. Using a mouse model of recurrent mammary tumorigenesis in combination with bioinformatics analyses of BC patients, Abravanel et al.
identified the role for Notch signaling in mammary tumor dormancy and recurrence using MMTV-rtTA; TetO-HER2/neu mice . They found that 1) Notch signaling was acutely upregulated in tumor cells following HER2 Cited by: 8.
The Notch signaling pathway is a critical regulator of cell fate determination conserved through evolution. Aberrant Notch signaling is associated with a wide range of human disorders from developmental syndromes to cancer. 13 Notch signaling is involved in the fate determination of a variety of cell types, including hematopoietic cells where it participates in differentiation, proliferation Cited by: Notch signaling is an evolutionarily conserved mechanism for specifying and regulating organogenesis.
Human and mouse genetic studies have demonstrated myriad mutations in the Notch signaling pathway that causes skeletal defects [19,20]. Previous studies showed conflicting results on the role of Notch signaling in bone homeostasis with either Author: Sung-Tzu Liang, Jung-Ren Chen, Jhih-Jie Tsai, Yu-Heng Lai, Chung-Der Hsiao.
Constitutive Notch activation increases numbers of embryonic mast cells, which can be abrogated by pharmacologic inhibition of Notch signaling.
To complement Notch pathway knockdown assays, we examined the mast cell phenotype in the context of Notch pathway hyperactivation using a transgenic zebrafish line overexpressing by: Multiple studies using animal models have demonstrated that Notch signaling is one of the critical regulators in cartilage homeostasis and joint maintenance.
Notch signaling components are expressed in adult articular cartilage, and the majority of chondrocytes residing in Author: Jennifer T. Zieba, Yi-Ting Chen, Brendan H. Lee, Yangjin Bae. Genetically engineered mice provide the most efficient and cost-effective models to study Notch signaling in a mammalian system.
Here, we review the various types of genetic models, tools, and strategies to study Notch signaling in mice, and provide examples of their by: 2.
Detailed narratives of mouse models of breast cancer from the mid-nineteenth century up to recent years have been elegantly provided by R.
Cardiff and D. Medina [20, 21].The first studies of mouse mammary cancer were performed on spontaneous tumors, mostly those involving the mouse mammary tumor virus (MMTV) or other oncogenic viruses that trigger mammary cancers in certain Cited by: 1.
To date, mutations disrupting multiple molecules and pathways such as Notch signaling pathway have been found to cause human CS 2,8,9,10,11, however, Author: Xianding Sun, Yang Zhou, Ruobin Zhang, Zuqiang Wang, Meng Xu, Dali Zhang, Junlan Huang, Fengtao Luo.
Mutation within an ubiquitin E3 ligase gene can lead to a failure in Notch signaling, excessive neurons, and depletion of neural progenitor cells in mind bomb mutants. Using mib hi zebrafish, we reported seizures and a down‐regulation of γ‐aminobutyric acid (GABA) signaling pathway genes.
A transcriptome analysis also identified differential expression pattern of genes related to Notch Cited by: INTRODUCTION. The Notch signaling pathway is widely conserved among metazoans. Vertebrate genomes contain several Notch paralogs, which control key developmental decisions at numerous stages and in diverse tissues and organs (Andersson et al., ; Gazave et al., ).The Notch pathway is ideally suited for signaling between adjacent cells because both the Notch receptor Cited by: Mechanosensory hair cells within the zebrafish lateral line spontaneously regenerate after aminoglycoside-induced death.
Exposure of 5-d-old larvae to μm neomycin for 1 h results in death of almost all lateral line hair cells. Regeneration of new hair cells is observed by 24 h after neomycin treatment with nearly complete replacement by 72 by: The first transgenic mouse expressing oncogenic rat neu (neuNT) was reported.
31 Unlike the stochastic occurrence of solitary mammary tumors in transgenic mice bearing the MMTV‐c‐myc or v‐Ha‐ras oncogenes, transgenic mice uniformly expressing the MMTV‐neuNT gene developed multifocal mammary tumors at the median age of days in FVB Cited by: 8.
Infection with Helicobacter pylori is a major risk factor for the development of gastric cancer, and infection with strains carrying the virulence factor CagA significantly increases this risk.
To investigate the mechanisms by which CagA promotes carcinogenesis, we generated transgenic zebrafish expressing CagA ubiquitously or in the anterior by: Angiogenesis, a natural phenomenon of developing new blood vessels, is an integral part of normal developmental processes as well as numerous pathological states in humans.
The angiogenic assays are reliable predictors of certain pathologies in particular tumor growth, metastasis, inflammation, wound healing, tissue regeneration, ischemia, cardiovascular, and ocular : Imran Shahid, Waleed H.
AlMalki, Mohammed W. AlRabia, Muhammad Ahmed, Mohammad T. Imam, Muhammed K. The liver has the remarkable capacity to regenerate through cellular division of hepatocytes. However, following severe injuries that abrogates the replicative capacity of hepatocytes some immature-like cells proliferate around the portal area and invade the parenchyma in a process known as ductular reaction (DR).
In humans, DR is observed in virtually all chronic liver disorders although the Cited by: 1. In pronephric development in Xenopus, Notch signaling also regulates the patterning of proximal versus distal tubule types (McLaughlin et al., ). Together, these studies point to a role for Notch signaling in nephron precursor structures (S-shaped bodies or their equivalents) in broadly defining major nephron segments and by: Using these novel transgenic tools, we were able to analyze in detail the interdependency between these two factors and their relationship with the Notch signaling pathway.
We also demonstrate that nkx expression persists in the adult ductal tree, notably in the centroacinar/terminal end duct cells (CACs), for which we show that they are Cited by: While Wnt/β-catenin signaling is known to be involved in the development of neural crest cells in zebrafish, it is unclear which Wnts are involved, and when they are required.
To address these issues we employed a zebrafish line that was transgenic for an inducible inhibitor of Wnt/β-catenin signaling, and inhibited endogenous Wnt/β-catenin signaling at discrete times in development.
Using Cited by: