scholarly journals Comparative analysis of CreER transgenic mice for the study of brain macrophages – a case study

2019 ◽  
Author(s):  
Louise Chappell-Maor ◽  
Masha Kolesnikov ◽  
Jonathan Grozovski ◽  
Jung-Seok Kim ◽  
Anat Shemer ◽  
...  

AbstractConditional mutagenesis and fate mapping have contributed considerably to our understanding of physiology and pathology. Specifically, Cre recombinase-based approaches allow the definition of cell type-specific contributions to disease development and inter-cellular communication circuits in respective animals models. Here we compared Cx3cr1CreER and Sall1CreER transgenic mice and their use to decipher the brain macrophage compartment as a showcase to discuss recent technological advances. Specifically, we highlight the need to define the accuracy of Cre recombinase expression, as well as strengths and pitfalls of these particular systems that should be taken into consideration when applying these models.

2020 ◽  
Vol 50 (3) ◽  
pp. 353-362 ◽  
Author(s):  
Louise Chappell‐Maor ◽  
Masha Kolesnikov ◽  
Jung‐Seok Kim ◽  
Anat Shemer ◽  
Zhana Haimon ◽  
...  

Author(s):  
Louise Chappell‐Maor ◽  
Masha Kolesnikov ◽  
Jung‐Seok Kim ◽  
Anat Shemer ◽  
Zhana Haimon ◽  
...  

Author(s):  
Yolanda Cortés-Alvarez ◽  
Rafael Estrella-Velázquez ◽  
Aarón Ivan González-Neri ◽  
Quezada-Moreno Maribel

This research points out how valuable the brain in humans is, it indicates from the definition of the word brain, of the nervous system, composition of the skull, parts of the brain, responsibilities of the brain, actions to keep the brain in good shape, the power that he has the brain and the senses that he indicates himself. There is a case study of an accident that caused a severe craniocerebral trauma teacher and the sequelae that will already be part of her teacher's daily life and the knowledge that these sequelae may continue to appear during the 3 years of the accident. It also presents the progress that has been achieved over 10 months of recovery, this with the aim of creating awareness in people and understanding how important the brain is to continue living in this magnificent world.


2005 ◽  
Vol 289 (6) ◽  
pp. R1763-R1769 ◽  
Author(s):  
Mikhiela Sherrod ◽  
Deborah R. Davis ◽  
Xizhou Zhou ◽  
Martin D. Cassell ◽  
Curt D. Sigmund

Angiotensinogen (AGT) is mainly expressed in glial cells in close proximity to renin-expressing neurons in the brain. We previously reported that glial-specific overexpression of ANG II results in mild hypertension. Here, we tested the hypothesis that glial-derived AGT plays an important role in blood pressure regulation in hypertensive mice carrying human renin (hREN) and human AGT transgenes under the control of their own endogenous promoters. To perform a glial-specific deletion of AGT, we used an AGT transgene containing loxP sites (hAGTflox), so the gene can be permanently ablated in the presence of cre-recombinase expression, driven by the glial fibrillary acidic protein (GFAP) promoter. Triple transgenic mice (RAC) containing a: 1) systemically expressed hREN transgene, 2) systemically expressed hAGTflox transgene, and 3) GFAP-cre-recombinase were generated and compared with double transgenic mice (RA) lacking cre-recombinase. Liver and kidney hAGT mRNA levels were unaltered in RAC and RA mice, as was the level of hAGT in the systemic circulation, consistent with the absence of cre-recombinase expression in those tissues. Whereas hAGT mRNA was present in the brain of RA mice (lacking cre-recombinase), it was absent from the brain of RAC mice expressing cre-recombinase, confirming brain-specific elimination of AGT. Immunohistochemistry revealed a loss of AGT immunostaining glial cells throughout the brain in RAC mice. Arterial pressure measured by radiotelemetry was significantly lower in RAC than RA mice and unchanged from nontransgenic control mice. These data suggest that there is a major contribution of glial-AGT to the hypertensive state in mice carrying systemically expressed hREN and hAGT genes and confirm the importance of a glial source of ANG II substrate in the brain.


2018 ◽  
Author(s):  
Anat Shemer ◽  
Jonathan Grozovski ◽  
Tuan Leng Tay ◽  
Jenhan Tao ◽  
Alon Volaski ◽  
...  

AbstractMicroglia are yolk sac-derived macrophages residing in the parenchyma of brain and spinal cord, where they interact with neurons and other glial cells by constantly probing their surroundings with dynamic extensions. Following different conditioning paradigms and bone marrow (BM) / hematopoietic stem cell (HSC) transplantation, graft-derived cells seed the brain and persistently contribute to the parenchymal brain macrophage compartment. Here we establish that these cells acquire over time microglia characteristics, including ramified morphology, longevity, radio-resistance and clonal expansion. However, even following prolonged CNS residence, transcriptomes and epigenomes of engrafted HSC-derived macrophages remain distinct from yolk sac-derived host microglia. Furthermore, BM graft-derived cells display discrete responses to peripheral endotoxin challenge, as compared to host microglia. Also in human HSC transplant recipients, engrafted cells remain distinct from host microglia, extending our finding to clinical settings. Collectively, our data emphasize the molecular and functional heterogeneity of parenchymal brain macrophages and highlight potential clinical implications for patients treated by HSC gene therapy.


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