Genetically engineered mice demonstrate that adenosine deaminase is essential for early postimplantation development

Development ◽  
1997 ◽  
Vol 124 (16) ◽  
pp. 3089-3097 ◽  
Author(s):  
M.R. Blackburn ◽  
T.B. Knudsen ◽  
R.E. Kellems
Keyword(s):  
Adenosine Deaminase ◽  
Genetically Modified ◽  
Genetically Engineered ◽  
Purine Metabolism ◽  
Trophoblast Cells ◽  
Relative Contribution ◽  
Decidual Cells ◽  
Genetically Engineered Mice ◽  
Essential Enzyme ◽  
Maternal Fetal Interface

Adenosine deaminase (ADA) is an essential enzyme of purine metabolism that is enriched at the maternal-fetal interface of mice throughout postimplantation development. During early postimplantation stages Ada is highly expressed in both maternally derived decidual cells and zygotically derived trophoblast cells. For the current study we utilized genetically modified mice to delineate the relative contribution and importance of decidual and trophoblast ADA at the maternal-fetal interface. In females genetically engineered to lack decidual ADA a striking pattern of expression was revealed in giant trophoblast cells that surround the early postimplantation embryo. Embryos within gestation sites lacking both decidual and trophoblast ADA died during the early postimplantation period, whereas expression in trophoblast cells alone was sufficient for survival through this period. Severe disturbances in purine metabolism were observed in gestation sites lacking decidual ADA, including the accumulation of the potentially toxic ADA substrates adenosine and 2′-deoxyadenosine. These experiments provide genetic evidence that Ada expression at the maternal-fetal interface is essential for early postimplantation development in mice.

213. Chemokines: key players at the maternal - fetal interface

2008 ◽  
Vol 20 (9) ◽  
pp. 13
Author(s):  
N. J. Hannan ◽  
L. A. Salamonsen
Keyword(s):  
Extracellular Matrix ◽  
Real Time ◽  
Extracellular Matrix Protein ◽  
Leukocyte Trafficking ◽  
Trophoblast Cells ◽  
Rt Pcr ◽  
Human Trophoblast ◽  
Decidual Cells ◽  
Trophoblast Migration ◽  
Maternal Fetal Interface

Establishment of pregnancy requires extensive communication at the maternal-fetal interface and involves a plethora of locally acting molecules, including the chemokines. Chemokines are multifunctional molecules initially described for roles in leukocyte trafficking, but since found to participate in many other processes such as differentiation and directed migration. Previously we have shown that the chemokines, CX3CL1 and CCL14, are abundant in human endometrial vasculature, leukocytes, epithelial and decidual cells at the time of implantation and that their receptors, CX3CR1 and CCR1, are present on invading human trophoblast. CX3CL1 and CCL14 directly promote human trophoblast migration. We hypothesised that these endometrial chemokines promote trophoblast migration by regulating adhesion molecules and extracellular matrix (ECM) components on the trophoblast, similar to mechanisms used in leukocyte trafficking. Trophoblast cells (AC1M-88) used previously, showed a marked increase in adhesion to fibronectin following treatment with CX3CL1 and CCL14. Alterations in trophoblast adhesion associated and ECM genes following chemokine stimulation were examined using pathway specific oligo-arrays and quantitative real-time RT–PCR. Over 30 transcripts were affected by CX3CL1 treatment and 15 were regulated by CCL14 treatment. Real-time RT–PCR confirmed significant changes in the mRNA transcripts of α-catenin (CTNNA1), extracellular matrix protein-1 (ECM1), osteopontin (SPP1), integrin α6 (ITGA6), matrix metalloproteinase-12 (MMP12) and integrin β5 (ITGB5) following chemokine treatment. Several of these molecules have previously been implicated in implantation. Immunohistochemistry confirmed the presence of integrin α6, SPP1 and ECM1 protein in first trimester human implantation sites. The temporal and spatial expression of chemokines, their receptors and adhesion related molecules at the maternal-fetal interface emphasises an important role in the controlled directional migration of trophoblast through the maternal decidua. For the first time this study demonstrates direct effects of CX3CL1 and CCL14 on trophoblast adhesion and ECM molecules suggesting mechanisms by which trophoblast cells migrate during early pregnancy.

scholarly journals The Cytokine Gene CXCL14 Restricts Human Trophoblast Cell Invasion by Suppressing Gelatinase Activity

Endocrinology ◽  
2009 ◽  
Vol 150 (12) ◽  
pp. 5596-5605 ◽  
Author(s):  
HaiBin Kuang ◽  
Qi Chen ◽  
Ying Zhang ◽  
Li Zhang ◽  
HongYing Peng ◽  
...  
Keyword(s):  
Trophoblast Cell ◽  
Trophoblast Invasion ◽  
Trophoblast Cells ◽  
Human Trophoblast ◽  
Gelatinase Activity ◽  
Invasion And Migration ◽  
Human Pregnancy ◽  
Decidual Cells ◽  
And Migration ◽  
Maternal Fetal Interface

Abstract Well-controlled trophoblast invasion into uterine decidua is a critical process for the normal development of placenta, which is tightly regulated by various factors produced within the trophoblast-endometrial microenvironment. CXCL14 is involved in tumor growth and metastasis, and its expression in placenta is temporally regulated during pregnancy. However, the role of CXCL14 in trophoblast function during human pregnancy is not clear. In this study, by using RT-PCR through human pregnancy, we found that CXCL14 was selectively expressed at early but not late pregnancy. Immunostaining revealed that CXCL14 proteins were strongly expressed in villous cytotrophoblasts and moderately in decidualized stromal cells but very weakly in syncytiotrophoblasts and extravillous trophoblasts. The effect of CXCL14 on trophoblast invasion were examined by using human villous explants cultured on Matrigel and further proved by invasion and migration assay of primary trophoblast cells and trophoblast cell line HTR-8/SVneo. Our data showed that CXCL14 significantly inhibited outgrowth of villous explant in vitro; this effect is due to suppression of trophoblast invasion and migration through regulating matrix metalloproteinases activities, whereas the trophoblast proliferation was not affected. Moreover, because a receptor for CXCL14 has not been identified, we performed further cell-specific CXCL14 binding activities with regard to different cell types within the maternal-fetal interface. Our data revealed that CXCL14 could specifically bind to trophoblast cells but not decidual cells from the maternal-fetal interface. These results suggest that CXCL14 plays an important role in regulating trophoblast invasion through an autocrine/paracrine manner during early pregnancy.

scholarly journals Toxicity modelling of Plk1-targeted therapies in genetically engineered mice and cultured primary mammalian cells

2011 ◽  
Vol 2 (1) ◽  
Author(s):  
Monika Raab ◽  
Sven Kappel ◽  
Andrea Krämer ◽  
Mourad Sanhaji ◽  
Yves Matthess ◽  
...  
Keyword(s):  
Targeted Therapies ◽  
Mammalian Cells ◽  
Genetically Engineered ◽  
Genetically Engineered Mice

scholarly journals Tenascin-C in Heart Diseases—The Role of Inflammation

2021 ◽  
Vol 22 (11) ◽  
pp. 5828
Author(s):  
Kyoko Imanaka-Yoshida
Keyword(s):  
Ventricular Remodeling ◽  
Heart Diseases ◽  
Genetically Engineered ◽  
Matricellular Protein ◽  
Myocardial Repair ◽  
Inflammatory Reactions ◽  
Tenascin C ◽  
Genetically Engineered Mice

Tenascin-C (TNC) is a large extracellular matrix (ECM) glycoprotein and an original member of the matricellular protein family. TNC is transiently expressed in the heart during embryonic development, but is rarely detected in normal adults; however, its expression is strongly up-regulated with inflammation. Although neither TNC-knockout nor -overexpressing mice show a distinct phenotype, disease models using genetically engineered mice combined with in vitro experiments have revealed multiple significant roles for TNC in responses to injury and myocardial repair, particularly in the regulation of inflammation. In most cases, TNC appears to deteriorate adverse ventricular remodeling by aggravating inflammation/fibrosis. Furthermore, accumulating clinical evidence has shown that high TNC levels predict adverse ventricular remodeling and a poor prognosis in patients with various heart diseases. Since the importance of inflammation has attracted attention in the pathophysiology of heart diseases, this review will focus on the roles of TNC in various types of inflammatory reactions, such as myocardial infarction, hypertensive fibrosis, myocarditis caused by viral infection or autoimmunity, and dilated cardiomyopathy. The utility of TNC as a biomarker for the stratification of myocardial disease conditions and the selection of appropriate therapies will also be discussed from a clinical viewpoint.

scholarly journals Characterization and visualization of murine coagulation factor VIII-producing cells in vivo

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Morisada Hayakawa ◽  
Asuka Sakata ◽  
Hiroko Hayakawa ◽  
Hikari Matsumoto ◽  
Takafumi Hiramoto ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Factor Viii ◽  
Fluorescent Protein ◽  
Coagulation Factor ◽  
Coagulation Factors ◽  
Genetically Engineered ◽  
Coagulation Factor Viii ◽  
Liver Sinusoidal Endothelial Cells ◽  
Genetically Engineered Mice

AbstractCoagulation factors are produced from hepatocytes, whereas production of coagulation factor VIII (FVIII) from primary tissues and cell species is still controversial. Here, we tried to characterize primary FVIII-producing organ and cell species using genetically engineered mice, in which enhanced green fluorescent protein (EGFP) was expressed instead of the F8 gene. EGFP-positive FVIII-producing cells existed only in thin sinusoidal layer of the liver and characterized as CD31high, CD146high, and lymphatic vascular endothelial hyaluronan receptor 1 (Lyve1)+. EGFP-positive cells can be clearly distinguished from lymphatic endothelial cells in the expression profile of the podoplanin− and C-type lectin-like receptor-2 (CLEC-2)+. In embryogenesis, EGFP-positive cells began to emerge at E14.5 and subsequently increased according to liver maturation. Furthermore, plasma FVIII could be abolished by crossing F8 conditional deficient mice with Lyve1-Cre mice. In conclusion, in mice, FVIII is only produced from endothelial cells exhibiting CD31high, CD146high, Lyve1+, CLEC-2+, and podoplanin− in liver sinusoidal endothelial cells.

scholarly journals Immune Competency of a Hairless Mouse Strain for Improved Preclinical Studies in Genetically Engineered Mice

2010 ◽  
Vol 9 (8) ◽  
pp. 2354-2364 ◽  
Author(s):  
Beverly S. Schaffer ◽  
Marcia H. Grayson ◽  
Joy M. Wortham ◽  
Courtney B. Kubicek ◽  
Amanda T. McCleish ◽  
...  
Keyword(s):  
Mouse Strain ◽  
Hairless Mouse ◽  
Genetically Engineered ◽  
Preclinical Studies ◽  
Genetically Engineered Mice ◽  
Immune Competency

scholarly journals miR-146a is a significant brake on autoimmunity, myeloproliferation, and cancer in mice

2011 ◽  
Vol 208 (6) ◽  
pp. 1189-1201 ◽  
Author(s):  
Mark P. Boldin ◽  
Konstantin D. Taganov ◽  
Dinesh S. Rao ◽  
Lili Yang ◽  
Jimmy L. Zhao ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Immune Cell ◽  
Myeloid Cell ◽  
Genetically Engineered ◽  
Biological Processes ◽  
Targeted Deletion ◽  
Genetically Engineered Mice ◽  
Immune Defects ◽  
Molecular Brake

Excessive or inappropriate activation of the immune system can be deleterious to the organism, warranting multiple molecular mechanisms to control and properly terminate immune responses. MicroRNAs (miRNAs), ∼22-nt-long noncoding RNAs, have recently emerged as key posttranscriptional regulators, controlling diverse biological processes, including responses to non-self. In this study, we examine the biological role of miR-146a using genetically engineered mice and show that targeted deletion of this gene, whose expression is strongly up-regulated after immune cell maturation and/or activation, results in several immune defects. Collectively, our findings suggest that miR-146a plays a key role as a molecular brake on inflammation, myeloid cell proliferation, and oncogenic transformation.

scholarly journals Development of a transplantable glioma tumour model from genetically engineered mice: MRI/MRS/MRSI characterisation

2016 ◽  
Vol 129 (1) ◽  
pp. 67-76 ◽  
Author(s):  
Magdalena Ciezka ◽  
Milena Acosta ◽  
Cristina Herranz ◽  
Josep M. Canals ◽  
Martí Pumarola ◽  
...  
Keyword(s):  
Genetically Engineered ◽  
Tumour Model ◽  
Genetically Engineered Mice
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