@article{ChubanovFerioliWisnowskyetal.2016,
  author    = {Chubanov, Vladimir and Ferioli, Silvia and Wisnowsky, Annika and Simmons, David G. and Leitzinger, Christin and Einer, Claudia and Jonas, Wenke and Shymkiv, Yuriy and Gudermann, Thomas and Bartsch, Harald and Braun, Attila and Akdogan, Banu and Mittermeier, Lorenz and Sytik, Ludmila and Torben, Friedrich and Jurinovic, Vindi and van der Vorst, Emiel P. C. and Weber, Christian and Yildirim, {\"O}nder A. and Sotlar, Karl and Sch{\"u}rmann, Annette and Zierler, Susanna and Zischka, Hans and Ryazanov, Alexey G.},
  title     = {Epithelial magnesium transport by TRPM6 is essential for prenatal development and adult survival},
  series = {eLife},
  volume    = {5},
  journal   = {eLife},
  doi       = {10.7554/eLife.20914},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-164987},
  pages     = {e19686},
  year      = {2016},
  abstract  = {Mg2+ regulates many physiological processes and signalling pathways. However, little is known about the mechanisms underlying the organismal balance of Mg2+. Capitalizing on a set of newly generated mouse models, we provide an integrated mechanistic model of the regulation of organismal Mg2+ balance during prenatal development and in adult mice by the ion channel TRPM6. We show that TRPM6 activity in the placenta and yolk sac is essential for embryonic development. In adult mice, TRPM6 is required in the intestine to maintain organismal Mg2+ balance, but is dispensable in the kidney. Trpm6 inactivation in adult mice leads to a shortened lifespan, growth deficit and metabolic alterations indicative of impaired energy balance. Dietary Mg2+ supplementation not only rescues all phenotypes displayed by Trpm6-deficient adult mice, but also may extend the lifespan of wildtype mice. Hence, maintenance of organismal Mg2+ balance by TRPM6 is crucial for prenatal development and survival to adulthood.},
  language  = {en}
}
@article{NagyvanGeffenStegneretal.2019,
  author    = {Nagy, Magdolna and van Geffen, Johanna P. and Stegner, David and Adams, David J. and Braun, Attila and de Witt, Susanne M. and Elvers, Margitta and Geer, Mitchell J. and Kuijpers, Marijke J. E. and Kunzelmann, Karl and Mori, Jun and Oury, C{\´e}cile and Pircher, Joachim and Pleines, Irina and Poole, Alastair W. and Senis, Yotis A. and Verdoold, Remco and Weber, Christian and Nieswandt, Bernhard and Heemskerk, Johan W. M. and Baaten, Constance C. F. M. J.},
  title     = {Comparative Analysis of Microfluidics Thrombus Formation in Multiple Genetically Modified Mice: Link to Thrombosis and Hemostasis},
  series = {Frontiers in Cardiovascular Medicine},
  volume    = {6},
  journal   = {Frontiers in Cardiovascular Medicine},
  doi       = {10.3389/fcvm.2019.00099},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-232194},
  year      = {2019},
  abstract  = {Genetically modified mice are indispensable for establishing the roles of platelets in arterial thrombosis and hemostasis. Microfluidics assays using anticoagulated whole blood are commonly used as integrative proxy tests for platelet function in mice. In the present study, we quantified the changes in collagen-dependent thrombus formation for 38 different strains of (genetically) modified mice, all measured with the same microfluidics chamber. The mice included were deficient in platelet receptors, protein kinases or phosphatases, small GTPases or other signaling or scaffold proteins. By standardized re-analysis of high-resolution microscopic images, detailed information was obtained on altered platelet adhesion, aggregation and/or activation. For a subset of 11 mouse strains, these platelet functions were further evaluated in rhodocytin- and laminin-dependent thrombus formation, thus allowing a comparison of glycoprotein VI (GPVI), C-type lectin-like receptor 2 (CLEC2) and integrin α6β1 pathways. High homogeneity was found between wild-type mice datasets concerning adhesion and aggregation parameters. Quantitative comparison for the 38 modified mouse strains resulted in a matrix visualizing the impact of the respective (genetic) deficiency on thrombus formation with detailed insight into the type and extent of altered thrombus signatures. Network analysis revealed strong clusters of genes involved in GPVI signaling and Ca2+ homeostasis. The majority of mice demonstrating an antithrombotic phenotype in vivo displayed with a larger or smaller reduction in multi-parameter analysis of collagen-dependent thrombus formation in vitro. Remarkably, in only approximately half of the mouse strains that displayed reduced arterial thrombosis in vivo, this was accompanied by impaired hemostasis. This was also reflected by comparing in vitro thrombus formation (by microfluidics) with alterations in in vivo bleeding time. In conclusion, the presently developed multi-parameter analysis of thrombus formation using microfluidics can be used to: (i) determine the severity of platelet abnormalities; (ii) distinguish between altered platelet adhesion, aggregation and activation; and (iii) elucidate both collagen and non-collagen dependent alterations of thrombus formation. This approach may thereby aid in the better understanding and better assessment of genetic variation that affect in vivo arterial thrombosis and hemostasis.},
  language  = {en}
}