Transgenic mice overexpressing the full-length neurotrophin receptor trkB exhibit increased activation of the trkB–PLCγ pathway, reduced anxiety, and facilitated learning

2004 ◽  
Vol 26 (1) ◽  
pp. 166-181 ◽  
Author(s):  
Eija Koponen ◽  
Vootele Võikar ◽  
Ruusu Riekki ◽  
Tommi Saarelainen ◽  
Tuomas Rauramaa ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Full Length ◽  
Neurotrophin Receptor ◽  
Facilitated Learning

scholarly journals Transgenic Mice Expressing the Intracellular Domain of the p75 Neurotrophin Receptor Undergo Neuronal Apoptosis

1997 ◽  
Vol 17 (18) ◽  
pp. 6988-6998 ◽  
Author(s):  
Marta Majdan ◽  
Christian Lachance ◽  
Andrew Gloster ◽  
Raquel Aloyz ◽  
Christine Zeindler ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Neuronal Apoptosis ◽  
Neurotrophin Receptor ◽  
P75 Neurotrophin Receptor ◽  
Intracellular Domain

Abstract 2774: Coexpression of Delta16 isoform and full-length HER-2 in F1 hybrid transgenic mice: effects on tumor growth and malignancy

2014 ◽  
Author(s):  
Pier-Luigi Lollini ◽  
Valentina Grosso ◽  
Dario Ranieri ◽  
Arianna Palladini ◽  
Marianna Ianzano ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Tumor Growth ◽  
Full Length ◽  
F1 Hybrid ◽  
Her 2

scholarly journals Reversal of Cognitive Impairment in gp120 Transgenic Mice by the Removal of the p75 Neurotrophin Receptor

2019 ◽  
Vol 13 ◽  
Author(s):  
Andrew Speidell ◽  
Gino Paolo Asuni ◽  
Valeria Avdoshina ◽  
Serena Scognamiglio ◽  
Patrick Forcelli ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Transgenic Mice ◽  
Neurotrophin Receptor ◽  
P75 Neurotrophin Receptor

Vaccine Properties of a Novel Marker Gene-Free Recombinant Modified Vaccinia Ankara (MVA) Expressing Immunodominant CMV Antigens.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2858-2858
Author(s):  
Don J. Diamond ◽  
Zhongde Wang ◽  
Corinna La Rosa ◽  
Tumul Srivastava ◽  
Wendy Zhou ◽  
...  
Keyword(s):  
T Cell ◽  
Transgenic Mice ◽  
Marker Gene ◽  
Healthy Adults ◽  
Full Length ◽  
Early Gene ◽  
Tegument Protein ◽  
Foreign Gene ◽  
Solid Organ ◽  
Hematopoietic Stem

Abstract Human CMV continues to be a major risk factor in patients undergoing allogeneic hematopoietic stem cell (HSCT) and solid organ transplant (SOT), despite advancement of antiviral therapy. CMV tegument protein pp65 and CMV immediate early gene product IE1 are both considered immunodominant targets of cell-mediated immunity (CMI) and potentially capable of controlling CMV infection. Similar to healthy adults, CMV tegument protein pp65 and IE1 are frequently recognized by human CD4 and CD8 T cells in HCT and SOT recipients. To better assess their role in host defense, we have constructed a novel attenuated poxvirus (MVA) transfer vector named pZWIIA and generated a recombinant MVA (rMVA) expressing both full-length pp65 and exon4 of IE1 (pp65-IE1-MVA) at high levels, followed by the genetic removal of the bacterial marker gene used to distinguish recombinant forms during the screening process. Immunogenicity evaluation indicates that pp65-IE1-MVA not only can induce robust primary CMI to both antigens in HLA A2.1, B7 and A11 transgenic mice, but also can stimulate vigorous expansion of memory T lymphocyte responses to pp65 and IE1 in PBMC of CMV-positive donors. The recent discovery that additional early antigens of CMV are also well-recognized by healthy adults prompted us to include the IE2 antigen in the vaccine. Evaluation of in vivo immunogenicity of the vaccine expressing IE2 in both transgenic mice and in vitro antigenicity in human peripheral blood lymphocytes of HSCT and SOT recipients will be presented. A novel overlapping peptide library spanning full-length IE2 has been constructed in our laboratory, and used in conjunction with the vaccine expressing IE2, along with IE1 and pp65. Since MVA has a foreign gene capacity of over 30 kilobases (Kb), we have developed a strategy to maximize coverage of haplotypes through insertion of 6 additional antigens into novel insertion sites of the virus, for a total of just 12.0 Kb of the CMV genome. The selected antigens cover 83% of the population, while representing over 22% of the combined CD4 and CD8 T cell repertoire in seropositives. Our studies of the recognition of these antigens expressed in MVA and monitored with our own synthesized over-lapping peptide libraries in both HSCT and SOT recipients will be presented. These properties make the MVA-based vaccine ideal for the dual role of priming and boosting CMV-specific T cell immunity as a means to control CMV disease in recipients of HCT or SOT. pZWIIA alone or in combination with other MVA transfer vectors can be used to generate MVA based multiple-antigen vaccine which have application in vaccine development for a wide spectrum of infectious diseases and cancer.

Lethality of Mouse Tissue Factor Pathway Inhibitor Gene Disruption Is Rescued By Transgenic Human Tissue Factor Pathway Inhibitor Knock in

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3495-3495 ◽  
Author(s):  
Robert Pachlinger ◽  
Rudolf Hartmann ◽  
Andrea Kolm ◽  
Erwin Panholzer ◽  
Nadja Ullrich ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Tissue Factor ◽  
Tissue Factor Pathway Inhibitor ◽  
Full Length ◽  
Mouse Tissue ◽  
Alternative Mrna Splicing ◽  
Mouse Tissues ◽  
Tissue Factor Pathway ◽  
Exon 4 ◽  
Targeting Vector

Abstract Background: Tissue factor pathway inhibitor (TFPI) is a key regulator of the extrinsic coagulation pathway. It inhibits FXa generation by forming a quaternary complex containing factor VIIa (FVIIa), tissue factor (TF), factor Xa (FXa), and TFPI. Two TFPI isoforms, TFPI alpha (TFPI a) and TFPI beta (TFPI b), have been identified, which differ in their C-terminal part due to alternative mRNA splicing events. TFPI a consists of three Kunitz domains (KD), while TFPI b contains two KDs and a C terminal GPI anchor linking the protein to endothelial cell surface. Deletion of the first Kunitz domain of TFPI, which is present in TFPI a and TFPI b in mice is known to be incompatible with viability due to intrauterine lethality (Huang et al., 1997). Aim: To generate transgenic humanized TFPI mice in which mouse (m)-TFPI is entirely replaced by human (hu)-TFPI, in order to facilitate analysis of specific anti hu-TFPI antagonists without interference from m-TFPI. Methods: Integration of the targeting vector, consisting of the m TFPI signal sequence, followed by the human TFPI cDNA and subsequent breeding analysis, was followed by genomic PCR. A sophisticated breeding strategy was used to entirely delete m-TFPI exon 4, which encodes KD1, in humanized transgenic mice. Expression of hu-/m-TFPI a and b mRNAs was analyzed by reverse transcription, cloning, and sequencing of the obtained DNA fragments. Protein levels of hu- and m-TFPI in plasma of transgenic and wild-type (wt) mice were analyzed using species specific ELISAs. Immunoprecipitation experiments in plasma and various mouse tissues are being performed to obtain more information on the presence and distribution of the hu-TFPI protein in transgenic mice. Results: Homozygous humanized TFPI mice were viable and exhibited no obvious abnormalities. Animals showed normal litter size with equal numbers of female and male pups. Genomic PCRs revealed proper integration of the targeting vector into the mouse chromosome and the homozygous status with the expected deletion of m-TFPI exon 4. Expression analyses of humanized TFPI mice on mRNA level demonstrated the absence of full length m-TFPI a and the presence of the humanized TFPI mRNA. Alternative spliced m-TFPI b messages lacking exons three and four were identified, likely leading to a nonfunctional protein. Full length hu-TFPI a mRNA was detected in various tissues in the humanized TFPI mice. The TFPI protein level in plasma from humanized mice was below the detection limit of the ELISA and at least ~300 fold below that for wt mice. Conclusion: Low levels of hu-TFPI may compensate the function of m-TFPI in vivo and circumvent embryonic lethality. Furthermore, we established a new mouse model which allows the regulation of physiologic and pathologic pathways to be assessed at TFPI plasma concentrations below the limit of detection. Disclosures Hoellriegl: Baxalta Innovations GmbH: Employment. Scheiflinger:Baxalta Innovations GmbH: Employment.

Coexpression of mRNA for the full-length neurotrophin receptor trk-C and trk-A in favourable neuroblastoma

1997 ◽  
Vol 33 (12) ◽  
pp. 2058-2063 ◽  
Author(s):  
T Svensson ◽  
M Rydén ◽  
F.H Schilling ◽  
C Dominici ◽  
R Sehgal ◽  
...  
Keyword(s):  
Full Length ◽  
Neurotrophin Receptor ◽  
Trk A

scholarly journals Neurotrophin/receptor expression in urinary bladder of mice with overexpression of NGF in urothelium

2011 ◽  
Vol 300 (2) ◽  
pp. F345-F355 ◽  
Author(s):  
Beatrice M. Girard ◽  
Susan E. Malley ◽  
Margaret A. Vizzard
Keyword(s):  
Growth Factor ◽  
Urinary Bladder ◽  
Transgenic Mice ◽  
Protein Expression ◽  
Neurotrophic Factor ◽  
Growth Factor Receptor ◽  
Receptor Expression ◽  
Bladder Function ◽  
Neurotrophin Receptor ◽  
Neuronal Sprouting

Urothelium-specific overexpression of nerve growth factor (NGF) in the urinary bladder of transgenic mice stimulates neuronal sprouting in the urinary bladder, produces increased voiding frequency, and results in increased referred somatic hypersensitivity. Additional NGF-mediated pleiotropic changes might contribute to the increased voiding frequency and pelvic hypersensitivity observed in these transgenic mice, such as modulation of other growth factor/receptor systems. Chronic overexpression of NGF in the urothelium was achieved through the use of a highly urothelium-specific uroplakin II promoter. In the present study, we examined NGF, brain-derived neurotrophic factor (BDNF), and associated receptor [p75NTR, tyrosine kinase (Trk)A, TrkB] transcript and protein expression in urothelium and detrusor smooth muscle of NGF-overexpressing (OE) and littermate wild-type mice, using real-time quantitative reverse transcription-polymerase chain reaction, ELISAs, and semiquantitation of immunohistochemistry. We focused on these growth factor/receptors given the established roles of NGF/TrkA, NGF/p75NTR, and BDNF/TrkB systems in bladder function. Increased voiding frequency in NGF-OE mice was confirmed by examining urination patterns. BDNF, TrkA, and TrkB protein expression was significantly ( P ≤ 0.01) reduced and p75NTR protein expression was significantly ( P ≤ 0.01) increased in urinary bladder of NGF-OE mice. The NGF-OE-induced changes in neurotrophic factor/receptor expression in urinary bladder may represent compensatory changes to reduce voiding frequency in the NGF-OE mouse.

ADAMTS13 Expressed In Platelets Offers Systemic Protection Against Arterial Thrombosis and Therapeutic Benefits In Murine Models Of Thrombotic Thrombocytopenic Purpura

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 446-446
Author(s):  
Brandy Pickens ◽  
Yingying Mao ◽  
X. Long Zheng
Keyword(s):  
Platelet Count ◽  
Transgenic Mice ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Arterial Thrombosis ◽  
Oxidative Injury ◽  
Therapeutic Benefit ◽  
Full Length ◽  
Murine Models ◽  
Wild Type ◽  
Thrombocytopenic Purpura

ADAMTS13, a plasma metalloprotease, cleaves von Willebrand factor (VWF) and inhibits arterial thrombosis and inflammatory response. Deficiency of plasma ADAMTS13, due hereditary mutations in ADAMTS13 gene or autoantibodies against ADAMTS13 protease, results in a potentially fatal syndrome, thrombotic thrombocytopenic purpura (TTP). Plasma infusion or exchange is the only effective therapy available to date. To develop novel therapeutics against TTP, we tested a hypothesis that recombinant ADAMTS13, expressed specifically in platelets, may offer systemic protection against arterial thrombosis and therefore provide therapeutic benefit for TTP. To test this hypothesis, we first generated transgenic mice (JAX B6SJL) carrying a human full-length ADAMTS13 gene under a murine platelet glycoprotein 1b (CD41) promoter. The transgenic mice were then bred with Adamts13-/- (CAST/Ei) mice for >4 generations. By Western blotting and activity assay, we show that a full-length human ADAMTS13 protein (∼195 kDa) and its proteolytic activity toward a FRETS-hVWF73 peptide are detected in platelet lysate obtained from transgenic (rA13-PltTG) mice but not in Adamts13-/- mice or wild-type mice. Little to no ADAMTS13 activity was detected in plasma in transgenic mice, suggesting the expressed human ADAMTS13 is stored inside platelets. ADAMTS13 was releasable upon stimulation with thrombin (1 U/ml), collagen (10 µg/ml), and AYPGKF (0.5 mM). More significantly, rA13-PltTG mice had higher baseline platelet count than Adamts13-/- mice, but exhibited a dramatically reduced rate of thrombus formation in mesenteric arterioles after oxidative injury with 10% ferric chloride as compared with Adamts13-/-mice and wild-type mice. Finally, rA13-PltTG mice were protected from Shigatoxin-2 (Stx-2) or murine recombinant VWF (mVWF)-induced “TTP-like” syndrome, as demonstrated by fewer rA13-PltTG mice having thrombocytopenia (defined by a 40% drop in platelet count from the baseline after challenge with Stx-2 or mVWF), faster and more complete recovery of thrombocytopenia, and significantly higher survival rate than Adamts13-/- mice. In summary, we have generated transgenic mice expressing human ADAMTS13 in platelets. Platelet ADAMTS13 is releasable upon stimulation by agonists and biologically functional in proteolytic cleavage of VWF in vitro. The platelet-derived ADAMTS13 offers systemic protection against arterial thrombosis after oxidative injury and provide a therapeutic benefit to murine models of TTP, resulting from hereditary ADAMTS13 deficiency. We are now in the process testing the efficacy of this strategy as a novel therapeutic for acquired TTP with inhibitors. Disclosures: No relevant conflicts of interest to declare.

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