scholarly journals Lymphocyte Activation Gene 3 (Lag3) Contributes to α-Synucleinopathy in α-Synuclein Transgenic Mice

2021 ◽  
Vol 15 ◽  
Author(s):  
Hao Gu ◽  
Xiuli Yang ◽  
Xiaobo Mao ◽  
Enquan Xu ◽  
Chen Qi ◽  
...  
Keyword(s):  
Mouse Model ◽  
Transgenic Mice ◽  
Disease Progression ◽  
Transgenic Mouse ◽  
Lewy Bodies ◽  
Lymphocyte Activation ◽  
Transgenic Mouse Model ◽  
Behavioral Deficits ◽  
Lymphocyte Activation Gene

Aggregation of misfolded α-synuclein (α-syn) is the major component of Lewy bodies and neurites in Parkinson’s disease (PD) and related α-synucleinopathies. Some α-syn mutations (e.g., A53T) in familial PD recapitulate the α-syn pathology in transgenic mice, which supports the importance of pathologic α-syn in driving the pathogenesis of α-synucleinopathies. Lymphocyte activation gene 3 (Lag3) is a receptor of α-syn fibrils facilitating pathologic α-syn spread; however, the role of Lag3 in mediating the pathogenesis in α-syn transgenic mice is not clear. Here, we report that depletion of Lag3 in human α-syn A53T transgenic (hA53T) mice significantly reduces the level of detergent-insoluble α-syn aggregates and phosphorylated ser129 α-syn, and inhibits activation of microglia and astrocytes. The absence of Lag3 significantly delays disease progression and reduces the behavioral deficits in hA53T transgenic mice leading to prolonged survival. Taken together, these results show that Lag3 contributes to the pathogenesis in the α-syn A53T transgenic mouse model.

scholarly journals Specific overexpression of IL-7 in the intestinal mucosa: the role in intestinal intraepithelial lymphocyte development

2008 ◽  
Vol 294 (6) ◽  
pp. G1421-G1430 ◽  
Author(s):  
Hua Yang ◽  
Blair Madison ◽  
Deborah L. Gumucio ◽  
Daniel H. Teitelbaum
Keyword(s):  
T Cell ◽  
Mouse Model ◽  
Transgenic Mice ◽  
Transgenic Mouse ◽  
Critical Role ◽  
Transgenic Mouse Model ◽  
Intraepithelial Lymphocytes ◽  
Specific Expression ◽  
And Function

IL-7 plays a crucial role in controlling T cell development and homeostasis. Since IL-7 may be derived from extraintestinal sources, and exogenous IL-7 broadly affects lymphoid populations, the actions of epithelial cell (EC)-derived IL-7 are not fully understood. The effect of intestinal specific expression of IL-7 on intestinal mucosal lymphocytes was investigated by using an IL-7 transgenic mouse model. We generated an intestinal EC-specific overexpressing IL-7 transgenic mouse model (IL-7vill) and compared their phenotype and function to wild-type C57BL/6J mice. EC-derived IL-7 overexpression was found to be exclusively in the small and large intestine. Numbers and subtypes of mucosal lymphocytes, including intraepithelial lymphocytes (IEL) and lamina propria lymphocytes (LPL), significantly changed in IL-7vill mice. From a functional standpoint, IEL proliferation also significantly increased in IL-7vill mice. IEL cytokine expression significantly changed in both T cell receptor (TCR)-αβ+ and TCR-γδ+ IEL subpopulations, including a significant increase in IFN-γ and TNF-α as well as an increase in keratinocyte growth factor expression. EC expression of CD103 (integrin αEβ7), the ligand of E-cadherin, markedly upregulated and may account for a mechanism of the massive expansion of IEL in transgenic mice. Systemic lymphoid populations did not change in transgenic mice. IL-7 overexpression by intestinal EC significantly affected IEL phenotype and function. These results offer insight into the role of IL-7 in IEL development and suggest a critical role of EC-derived expression of IL-7 in the phenotype and function of IEL.

scholarly journals Role of human group IIA secreted phospholipase A2 in malaria pathophysiology: Insights from a transgenic mouse model

Biochimie ◽  
2021 ◽  
Author(s):  
Mélanie Dacheux ◽  
Soraya Chaouch ◽  
Alonso Joy ◽  
Amandine Labat ◽  
Christine Payré ◽  
...  
Keyword(s):  
Mouse Model ◽  
Phospholipase A2 ◽  
Transgenic Mouse ◽  
Transgenic Mouse Model ◽  
Human Group ◽  
Secreted Phospholipase A2

scholarly journals Induced Disruption of the Iron-Regulatory Hormone Hepcidin Inhibits Acute Inflammatory Hypoferraemia

2016 ◽  
Vol 8 (5) ◽  
pp. 517-528 ◽  
Author(s):  
Andrew E. Armitage ◽  
Pei Jin Lim ◽  
Joe N. Frost ◽  
Sant-Rayn Pasricha ◽  
Elizabeth J. Soilleux ◽  
...  
Keyword(s):  
Mouse Model ◽  
Transgenic Mouse ◽  
Brucella Abortus ◽  
Serum Iron ◽  
Vibrio Vulnificus ◽  
Iron Status ◽  
Transgenic Mouse Model ◽  
Innate Immune ◽  
Serum Hepcidin

Withdrawal of iron from serum (hypoferraemia) is a conserved innate immune antimicrobial strategy that can withhold this critical nutrient from invading pathogens, impairing their growth. Hepcidin (Hamp1) is the master regulator of iron and its expression is induced by inflammation. Mice lacking Hamp1 from birth rapidly accumulate iron and are susceptible to infection by blood-dwelling siderophilic bacteria such as Vibrio vulnificus. In order to study the innate immune role of hepcidin against a background of normal iron status, we developed a transgenic mouse model of tamoxifen-sensitive conditional Hamp1 deletion (termed iHamp1-KO mice). These mice attain adulthood with an iron status indistinguishable from littermate controls. Hamp1 disruption and the consequent decline of serum hepcidin concentrations occurred within hours of a single tamoxifen dose. We found that the TLR ligands LPS and Pam3CSK4 and heat-killed Brucella abortus caused an equivalent induction of inflammation in control and iHamp1-KO mice. Pam3CSK4 and B. abortus only caused a drop in serum iron in control mice, while hypoferraemia due to LPS was evident but substantially blunted in iHamp1-KO mice. Our results characterise a powerful new model of rapidly inducible hepcidin disruption, and demonstrate the critical contribution of hepcidin to the hypoferraemia of inflammation.

Transgenic mouse model for evaluation of the role of cyclin-dependent kinase 8 in vascular disease

2021 ◽  
Vol 331 ◽  
pp. e62
Author(s):  
E. Varlamova ◽  
A. Bruter ◽  
V. Mogila ◽  
I. Roninson ◽  
A. Deykin
Keyword(s):  
Mouse Model ◽  
Vascular Disease ◽  
Transgenic Mouse ◽  
Transgenic Mouse Model ◽  
Cyclin Dependent Kinase

scholarly journals A Longitudinal Study of Behavioral Deficits in an AβPP Transgenic Mouse Model of Alzheimer's Disease

2011 ◽  
Vol 25 (2) ◽  
pp. 231-243 ◽  
Author(s):  
Daniel Havas ◽  
Birgit Hutter-Paier ◽  
Kiren Ubhi ◽  
Edward Rockenstein ◽  
Karl Crailsheim ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Longitudinal Study ◽  
Mouse Model ◽  
Transgenic Mouse ◽  
Transgenic Mouse Model ◽  
Behavioral Deficits ◽  
Model Of Alzheimer’S Disease

scholarly journals Functional and structural connectome properties in the 5XFAD transgenic mouse model of Alzheimer’s disease

2018 ◽  
Vol 2 (2) ◽  
pp. 241-258 ◽  
Author(s):  
Shelli R. Kesler ◽  
Paul Acton ◽  
Vikram Rao ◽  
William J. Ray
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Transgenic Mice ◽  
Transgenic Mouse ◽  
Amyloid Beta ◽  
Molecular Mechanisms ◽  
Diffusion Tensor ◽  
Transgenic Mouse Model ◽  
Structural Connectome

Neurodegeneration in Alzheimer’s disease (AD) is associated with amyloid-beta peptide accumulation into insoluble amyloid plaques. The five-familial AD (5XFAD) transgenic mouse model exhibits accelerated amyloid-beta deposition, neuronal dysfunction, and cognitive impairment. We aimed to determine whether connectome properties of these mice parallel those observed in patients with AD. We obtained diffusion tensor imaging and resting-state functional magnetic resonance imaging data for four transgenic and four nontransgenic male mice. We constructed both structural and functional connectomes and measured their topological properties by applying graph theoretical analysis. We compared connectome properties between groups using both binarized and weighted networks. Transgenic mice showed higher characteristic path length in weighted structural connectomes and functional connectomes at minimum density. Normalized clustering and modularity were lower in transgenic mice across the upper densities of the structural connectome. Transgenic mice also showed lower small-worldness index in higher structural connectome densities and in weighted structural networks. Hyper-correlation of structural and functional connectivity was observed in transgenic mice compared with nontransgenic controls. These preliminary findings suggest that 5XFAD mouse connectomes may provide useful models for investigating the molecular mechanisms of AD pathogenesis and testing the effectiveness of potential treatments.

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