The
| Autor: | Giada Di Nunzio, Mitchell J. Geer, Silke Heising, Arthur Weiss, Guillaume E. Desanti, Zoltan Nagy, Yotis A. Senis, Timo Vögtle, Jun Mori, Alexandra Mazharian, Alexander Tarakhovsky, Benjamin G. Neel, Ralph Gareus |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Genetically modified mouse Blood Platelets Agglutination Platelet Aggregation Transgene Immunology Inflammation Bone Marrow Cells Mice Transgenic 030204 cardiovascular system & hematology Biology Platelet Factor 4 Biochemistry CSK Tyrosine-Protein Kinase 03 medical and health sciences 0302 clinical medicine Megakaryocyte Conditional gene knockout medicine Recombinase Leukocytes Animals Homeostasis Cell Lineage Lymphocyte Count Cell Size Recombination Genetic Integrases Receptor-Like Protein Tyrosine Phosphatases Class 3 Gene targeting Cell Biology Hematology Platelets and Thrombopoiesis Phenotype Cell biology Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure src-Family Kinases Platelet Glycoprotein GPIb-IX Complex Gene Targeting Models Animal medicine.symptom Megakaryocytes Spleen |
| Zdroj: | Blood. 133(4) |
| ISSN: | 1528-0020 |
| Popis: | Conditional knockout (KO) mouse models are invaluable for elucidating the physiological roles of platelets. The Platelet factor 4-Cre recombinase (Pf4-Cre) transgenic mouse is the current model of choice for generating megakaryocyte/platelet-specific KO mice. Platelets and leukocytes work closely together in a wide range of disease settings, yet the specific contribution of platelets to these processes remains unclear. This is partially a result of the Pf4-Cre transgene being expressed in a variety of leukocyte populations. To overcome this issue, we developed a Gp1ba-Cre transgenic mouse strain in which Cre expression is driven by the endogenous Gp1ba locus. By crossing Gp1ba-Cre and Pf4-Cre mice to the mT/mG dual-fluorescence reporter mouse and performing a head-to-head comparison, we demonstrate more stringent megakaryocyte lineage-specific expression of the Gp1ba-Cre transgene. Broader tissue expression was observed with the Pf4-Cre transgene, leading to recombination in many hematopoietic lineages, including monocytes, macrophages, granulocytes, and dendritic and B and T cells. Direct comparison of phenotypes of Csk, Shp1, or CD148 conditional KO mice generated using either the Gp1ba-Cre or Pf4-Cre strains revealed similar platelet phenotypes. However, additional inflammatory and immunological anomalies were observed in Pf4-Cre-generated KO mice as a result of nonspecific deletion in other hematopoietic lineages. By excluding leukocyte contributions to phenotypes, the Gp1ba-Cre mouse will advance our understanding of the role of platelets in inflammation and other pathophysiological processes in which platelet-leukocyte interactions are involved. |
| Databáze: | OpenAIRE |
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