Expression data from Adam10 knock out mice and wild type
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE25480 | GEO | 2011/01/06
SECONDARY ACCESSION(S): PRJNA134615
REPOSITORIES: GEO
Similar Datasets
Project description:Adam10, a cell surface protease, cleaving many proteins including TNF-alpha and E-cadherin. Here we investigate the genome wide effects of Adam10 knock out on the transcriptome. Commercial microarrays (Affymetrix Mouse Gene ST 1.0) were used to generate genome wide mRNA profiles. Mouse tissue samples from n=4 wiltype skin and n=4 Adam10 knockout skin were used in the study.
2011-01-06 | E-GEOD-25480 | biostudies-arrayexpress
Project description:Disintegrin and metalloproteinases ADAM10 and ADAM17 can release the extracellular region of a variety of membrane-bound proteins including cytokines, adhesion molecules, growth factors and receptors, important for many biological functions (ectodomain shedding).. So far, substrate identification for ADAM10 and ADAM17 focused exclusively on their membrane-anchored forms and their function as sheddases. With ADAM8 we now describe the first protease capable of releasing the ADAM17 ectodomain. Based on these findings, we investigated whether the soluble ectodomains of ADAM10 and ADAM17 still exhibit shedding activity and to determine their soluble protein substrate pool . To address this, a mass spectrometry-based N-terminomics approach (TAILS) was used to identify potential targets of soluble ADAM10 and ADAM17 (sADAM10/17) within the secretome of the murine cardiomyocyte cell line HL-1. We identified almost 140 protein cleavage events in total and 45 common substrates for both sADAM10 and sADAM17. Further in-vitro studies confirmed fibronectin, cystatin C, sN-cadherin, PCPE-1 as well as sAPP as direct substrates of soluble ADAM10 and/or ADAM17. Overall, we present the first degradome study for sADAM10 and sADAM17, thereby introducing a new regulation mode of the proteolytic activity of these essential proteases within the protease web.
2019-06-24 | PXD013718 | Pride
Project description:Transcriptional profiling of mouse cartilage tissues comparing control and mutant mice (in which the Adam10 allele was excised under the control of a Col2a1 promoter) to negate ADAM10 activity in osteochondroprogenitors. Goal was to determine the effects of the loss of ADAM10 activity on cartilage gene expression.
2019-12-11 | GSE141743 | GEO
Project description:In a transgenic mouse model of Alzheimer disease (AD), cleavage of the amyloid precursor protein (APP) by the α-secretase ADAM10 prevented amyloid plaque formation and alleviated cognitive deficits. Furthermore, there was a positive influence of ADAM10 over-expression on neurotransmitter-specific formation of synapses and on synaptic plasticity. To assess the influence of ADAM10 on the gene expression profile in the brain we performed microarray analysis using RNA isolated from brains of five month old mice over-expressing either the α-secretase ADAM10 or a dominant-negative mutant (dn) of this enzyme. As compared to non-transgenic wild-type mice, 355 genes were found to be differentially expressed in ADAM10 transgenic mice and 143 genes in dnADAM10 mice. A higher number of genes was found to be differentially regulated in double-transgenic mouse strains additionally expressing the human APP V717I mutant (APP[V717I]). Thus, α-secretase cleavage of over-expressed APP[V717I] alters CNS gene expression additionally. Keywords: genetic modification
2009-01-22 | GSE10908 | GEO
Project description:Metzincin metalloproteases have major roles in intercellular communication by modulating the function of membrane proteins. One of the proteases is the a-disintegrin-and-metalloprotease 10 (ADAM10) which acts as alpha-secretase of the Alzheimer’s disease amyloid precursor protein. ADAM10 is also required for neuronal network functions in murine brain, but neuronal ADAM10 substrates are only partly known. With a proteomic analysis of Adam10-deficient neurons we identified 91, mostly novel ADAM10 substrate candidates, making ADAM10 a major protease for membrane proteins in the nervous system. Several novel substrates, including the neuronal cell adhesion protein NrCAM, are involved in brain development. Indeed, we detected mistargeted axons in the olfactory bulb of conditional ADAM10-/- mice, which correlate with reduced cleavage of NrCAM, NCAM and other ADAM10 substrates. In summary, the novel ADAM10 substrates provide a potential molecular basis for neuronal network dysfunctions in conditional ADAM10-/- mice and demonstrate a fundamental function of ADAM10 as a sheddase in the brain.
2018-10-18 | PXD003426 | Pride
Project description:Myocardial infarction (MI) contributes to cardiac mortality and morbidity. After myocardial infarction the innate immune response is pivotal in clearing of tissue debris as well as scar formation, but exaggerated cytokine and chemokine secretion with subsequent leukocyte infiltration also leads to further tissue damage. Post-translational regulation of cytokine / chemokine signaling occurs via ectodomain shedding through a disintegrin and metalloproteases (ADAMs). Here, we address the value of targeting a previously unknown ADAM10 / CX3CL1 axis in the regulation of neutrophil recruitment early after MI. We show that myocardial ADAM10 is distinctly upregulated in biopsies from patients with ischemia-driven cardiomyopathy and correlates with heart failure progression. Intriguingly, upon MI in mice, pharmacological treatment with the ADAM10 inhibitionor GI254023X as well as genetic cardiomycyte-specific ADAM10 deletion improves survival with markedly enhanced heart function and reduced scar size. Mechanistically, this is driven by abolished ADAM10-mediated CX3CL1 ectodomain shedding followed by diminished IL-1β-dependent inflammation, reduced neutrophil bone marrow egress as well as myocardial tissue infiltration. Genetic cardiomycyte-specific ADAM10 deletion confirmes the small-molecule data and leads to improved cardiac function and reduction in inflammatory markers after ischemic myocardial injury. Thus, our data shows a conceptual insight into how acute MI induces chemotactic signaling via ectodomain shedding in cardiomyocytes.
2022-11-10 | GSE217268 | GEO
Project description:The spleen contains phenotypically and functionally distinct cDC1 and cDC2 subpopulations, which each can be divided into several smaller and less-well characterized subsets. Despite advances in understanding the complexity of DC ontogeny and function by transcriptional programming, the significance of post-translational modifications in controlling tissue-specific cDC (subset) immunobiology remains elusive. Here, we identified the cell surface-expressed A-disintegrin-and-metalloproteinase 10 (ADAM10) as an essential regulator of cDC1 and cDC2 homeostasis in the splenic marginal zone (MZ). Mice with a CD11c-specific deletion of ADAM10 (ADAM10ΔCD11c) exhibited a complete loss of splenic ESAMhi cDC2A, because ADAM10 controlled their commitment, differentiation, survival, and EBI2-mediated localization within the MZ. Moreover, we discovered that ADAM10 is a molecular switch regulating cDC2 subset heterogeneity in the spleen, as this unbalanced cDC2A homeostasis in the absence of ADAM10 was compensated for by the emergence of a novel Clec12a+ cDC2B subset, closely resembling cDC2 generally found in peripheral lymph nodes. Moreover, in ADAM10ΔCD11c mice terminal differentiation of cDC1 was abrogated, resulting in reduced numbers of Langerin+ cDC1.
2023-06-27 | GSE154309 | GEO
Project description:The spleen contains phenotypically and functionally distinct cDC1 and cDC2 subpopulations, which each can be divided into several smaller and less-well characterized subsets. Despite advances in understanding the complexity of DC ontogeny and function by transcriptional programming, the significance of post-translational modifications in controlling tissue-specific cDC (subset) immunobiology remains elusive. Here, we identified the cell surface-expressed A-disintegrin-and-metalloproteinase 10 (ADAM10) as an essential regulator of cDC1 and cDC2 homeostasis in the splenic marginal zone (MZ). Mice with a CD11c-specific deletion of ADAM10 (ADAM10ΔCD11c) exhibited a complete loss of splenic ESAMhi cDC2A, because ADAM10 controlled their commitment, differentiation, survival, and EBI2-mediated localization within the MZ. Moreover, we discovered that ADAM10 is a molecular switch regulating cDC2 subset heterogeneity in the spleen, as this unbalanced cDC2A homeostasis in the absence of ADAM10 was compensated for by the emergence of a novel Clec12a+ cDC2B subset, closely resembling cDC2 generally found in peripheral lymph nodes. Moreover, in ADAM10ΔCD11c mice terminal differentiation of cDC1 was abrogated, resulting in reduced numbers of Langerin+ cDC1.
2021-09-06 | GSE154767 | GEO
Project description:To investigate the expression prolfile of genes regulated by ADAM10 in HRMVECs.
2024-07-24 | GSE245783 | GEO
Project description:A disintegrin and metalloprotease 10 (ADAM10) is essential for embryonic development and impacts on diseases such as cancer, Alzheimer’s and inflammatory diseases. ADAM10 is a ‘molecular scissor’ that proteolytically cleaves the extracellular region from over 100 substrates, including Notch, amyloid precursor protein, cadherins, growth factors and chemokines. ADAM10 was recently proposed to function as six distinct scissors with different substrates, depending on its association with one of six regulatory tetraspanins, termed TspanC8s. However, it remains unclear whether ADAM10 function is critically dependent on a TspanC8 partner. To address this, we generated the first monoclonal antibodies to Tspan15 as a model TspanC8. These were used to show that ADAM10 is the principal Tspan15-interacting protein, that Tspan15 expression requires ADAM10 in cell lines and primary cells, and that a synthetic ADAM10/Tspan15 fusion protein is a functional scissor. Together these findings suggest that ADAM10 exists as an ADAM10/TspanC8 scissor complex.
2021-08-24 | PXD016508 | Pride