scholarly journals Characterization of a Cyp2a(4/5)bgs ‐null Mouse Model: Role of CYP2A and CYP2B in Nicotine Metabolism

2012 ◽  
Vol 26 (S1) ◽  
Author(s):  
Lei Li ◽  
Yuan Wei ◽  
Xin Zhou ◽  
Lindsay B. Hough ◽  
Xinxin Ding
Keyword(s):  
Mouse Model ◽  
Null Mouse ◽  
Nicotine Metabolism

scholarly journals Depletion of Cholesteryl Esters Causes Meibomian Gland Dysfunction-Like Symptoms in a Soat1-Null Mouse Model

2021 ◽  
Vol 22 (4) ◽  
pp. 1583
Author(s):  
Igor A. Butovich ◽  
Amber Wilkerson ◽  
Seher Yuksel
Keyword(s):  
Mouse Model ◽  
High Resolution Mass Spectrometry ◽  
Meibomian Gland ◽  
Lipid Homeostasis ◽  
Null Mouse ◽  
Complete Suppression ◽  
Cholesteryl Esters ◽  
Wild Type ◽  
Massive Accumulation

Previous studies on ablation of several key genes of meibogenesis related to fatty acid elongation, omega oxidation, and esterification into wax esters have demonstrated that inactivation of any of them led to predicted changes in the meibum lipid profiles and caused severe abnormalities in the ocular surface and Meibomian gland (MG) physiology and morphology. In this study, we evaluated the effects of Soat1 ablation that were expected to cause depletion of the second largest class of Meibomian lipids (ML)—cholesteryl esters (CE)—in a mouse model. ML of the Soat1-null mice were examined using liquid chromatography high-resolution mass spectrometry and compared with those of Soat1+/− and wild-type mice. Complete suppression of CE biosynthesis and simultaneous accumulation of free cholesterol (Chl) were observed in Soat1-null mice, while Soat1+/− mutants had normal Chl and CE profiles. The total arrest of the CE biosynthesis in response to Soat1 ablation transformed Chl into the dominant lipid in meibum accounting for at least 30% of all ML. The Soat1-null mice had clear manifestations of dry eye and MG dysfunction. Enrichment of meibum with Chl and depletion of CE caused plugging of MG orifices, increased meibum rigidity and melting temperature, and led to a massive accumulation of lipid deposits around the eyes of Soat1-null mice. These findings illustrate the role of Soat1/SOAT1 in the lipid homeostasis and pathophysiology of MG.

scholarly journals Differential Requirements for VirB1 and VirB2 during Brucella abortus Infection

2004 ◽  
Vol 72 (9) ◽  
pp. 5143-5149 ◽  
Author(s):  
Andreas B. den Hartigh ◽  
Yao-Hui Sun ◽  
David Sondervan ◽  
Niki Heuvelmans ◽  
Marjolein O. Reinders ◽  
...  
Keyword(s):  
Mouse Model ◽  
Brucella Abortus ◽  
Persistent Infection ◽  
Host Cells ◽  
Intracellular Replication ◽  
Bacterial Surface ◽  
Type Iv

ABSTRACT The Brucella abortus virB operon, encoding a type IV secretion system (T4SS), is required for intracellular replication and persistent infection in the mouse model. The products of the first two genes of the virB operon, virB1 and virB2, are predicted to be localized at the bacterial surface, where they could potentially interact with host cells. Studies to date have focused on characterization of transposon mutations in these genes, which are expected to exert polar effects on downstream genes in the operon. In order to determine whether VirB1 and VirB2 are required for the function of the T4SS apparatus, we constructed and characterized nonpolar deletion mutations of virB1 and virB2. Both mutants were shown to be nonpolar, as demonstrated by their ability to express the downstream gene virB5 during stationary phase of growth in vitro. Both VirB1 and VirB2 were essential for intracellular replication in J774 macrophages. The nonpolar virB2 mutant was unable to cause persistent infection in the mouse model, demonstrating the essential role of VirB2 in the function of the T4SS apparatus during infection. In contrast, the nonpolar virB1 mutant persisted at wild-type levels, showing that the function of VirB1 is dispensable in the mouse model of persistent infection.

scholarly journals NLRP3- and AIM2-autonomy in a mouse model of MSU crystal-induced acute inflammation in vivo suggests imiquimod-dependent targeting of Il-1[beta] expression as relevant therapy for gout patients.

2019 ◽  
Author(s):  
Alexandre Mariotte ◽  
Aurore Decauwer ◽  
Chrystelle Po ◽  
Cherine Abou-Faycal ◽  
Angelique Pichot ◽  
...  
Keyword(s):  
Mouse Model ◽  
Acute Inflammation ◽  
Joint Inflammation ◽  
Inflammatory Action ◽  
Recognition Receptor ◽  
Msu Crystals

The role of Monosodium Urate (MSU) crystals in gout pathophysiology is well described, as is the major impact of IL-1b in the inflammatory reaction that constitutes the hallmark of the disease. However, despite the discovery of the NLRP3 inflammasome and its role as a Pattern Recognition Receptor linking the detection of a danger signal (MSU) to IL-1b; secretion in vitro, the precise mechanisms leading to joint inflammation in gout patients are still poorly understood. Here, we provide an extensive clinical, biological and molecular characterization of the acute uratic inflammation mouse model induced by subcutaneous injection of MSU crystals, which accurately mimics human gout. Our work reveals several key features of MSU-dependent inflammation and identifies novel therapeutic opportunities, among which the use of topical application of imiquimod to promote interferon-dependent anti-inflammatory action maybe relevant.

scholarly journals Generation and Characterization of a Novel Cyp2a(4/5)bgs-Null Mouse Model

2012 ◽  
Vol 41 (1) ◽  
pp. 132-140 ◽  
Author(s):  
Yuan Wei ◽  
Lei Li ◽  
Xin Zhou ◽  
Qing-Yu Zhang ◽  
Anwar Dunbar ◽  
...  
Keyword(s):  
Mouse Model ◽  
Null Mouse

scholarly journals Generation and Characterization of a Cyp4b1 Null Mouse and the Role of CYP4B1 in the Activation and Toxicity of Ipomeanol

2013 ◽  
Vol 134 (2) ◽  
pp. 243-250 ◽  
Author(s):  
Oliver T. Parkinson ◽  
H. Denny Liggitt ◽  
Allan E. Rettie ◽  
Edward J. Kelly
Keyword(s):  
Null Mouse

scholarly journals TLE4 Is a Critical Mediator of Osteoblast and Runx2-Dependent Bone Development

2021 ◽  
Vol 9 ◽  
Author(s):  
Thomas H. Shin ◽  
Evangelos Theodorou ◽  
Carl Holland ◽  
Rae’e Yamin ◽  
Cathleen L. Raggio ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Mouse Model ◽  
Bone Formation ◽  
Bone Development ◽  
Null Mouse ◽  
Bone Homeostasis ◽  
Multiple Processes ◽  
Hematopoietic Regulation ◽  
Bone Calcification

Healthy bone homeostasis hinges upon a delicate balance and regulation of multiple processes that contribute to bone development and metabolism. While examining hematopoietic regulation by Tle4, we have uncovered a previously unappreciated role of Tle4 on bone calcification using a novel Tle4 null mouse model. Given the significance of osteoblasts in both hematopoiesis and bone development, this study investigated how loss of Tle4 affects osteoblast function. We used dynamic bone formation parameters and microCT to characterize the adverse effects of Tle4 loss on bone development. We further demonstrated loss of Tle4 impacts expression of several key osteoblastogenic genes, including Runx2, Oc, and Ap, pointing toward a potential novel mechanism for Tle4-dependent regulation of mammalian bone development in collaboration with the RUNX family members.

scholarly journals Examining the Role of CD30 in an Anaplastic Large Cell Lymphoma Mouse Model

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2542-2542
Author(s):  
Teresa Poggio ◽  
Linda Graessel ◽  
Stefanie Kreutmair ◽  
Cornelius Miething ◽  
Dietmar Pfeifer ◽  
...  
Keyword(s):  
Immune System ◽  
T Cell ◽  
Mouse Model ◽  
Cell Lymphoma ◽  
Large Cell ◽  
Disease Development ◽  
Large Cell Lymphoma ◽  
The Impact

Anaplastic large cell lymphoma (ALCL) represents a heterogeneous group of T-cell non-Hodgkin lymphoma (NHL) mainly affecting children and young adults. About 70% of systemic ALCLs are associated with a characteristic chromosomal translocation, t(2;5)(p23;35) which fuses the anaplastic lymphoma kinase (ALK) gene on chromosome 2 with the nucleophosmin (NPM) gene on chromosome 5, resulting in the NPM-ALK fusion gene, its over-expression and constitutive kinase activity. Immunophenotypic characterization of human ALCL revealed highly CD30-positive cells of T- or Null-Cell-origin and resulted in promising clinical trials with CD30-coupled antibodies. However, the impact of CD30 on disease development remains unclear and the relationship between NPM-ALK and CD30 has been investigated mostly using cell line models. Syngeneic mouse models of cancer can serve as useful models since the tumors develop in situ where the contribution made by the immune system and the extracellular matrix can be investigated. Here, we focus on the involvement of CD30 in a retroviral murine bone marrow transplantation model of ALCL. In this model, the BM of Lck-Cre-transgenic mice is infected with a MSCV-Stop-NPM-ALK-IRES-EGFP vector leading to expression of NPM-ALK in early T-cells. With a latency of 3-4 months, mice develop lymphomas and die from neoplastic T-cell-infiltration of BM and lymphatic organs. To investigate the impact of abrogation of CD30 signals on the development of NPM-ALK+ ALCL in our model, CD30 knockout mice were crossed with Lck-Cre mice. Both Lck-Cre NPM-ALK CD30 wt and Lck-Cre NPM-ALK CD30 ko recipients develop a human ALCL-like lymphoma with a pure T-cell phenotype characterized by Thy1.2+ cells infiltrating the thymus, lymph nodes, spleen and BM. First results from Lck-Cre NPM-ALK CD30 ko transplanted mice showed impaired disease induction and prolonged survival compared to CD30 wt animals. Moreover, secondary transplantation of NPM-ALK thymic lymphomas led to distinct deceleration of disease development upon CD30 deletion. Microarray analyses have shed some light on the mechanisms underlying the delayed lymphoma progression of CD30 deleted tumors with an upregulation of inflammatory pathways and proteins that are master players in inflammation and immune responses. Further characterization of the role of CD30-mediated immune response in disease progression using this mouse model and immunocompromised mice is ongoing. An improved understanding of how the immune system affects tumor progression will extend the rationale in translational strategies to use immunotherapies for patients with T-NHLs. Disclosures No relevant conflicts of interest to declare.

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