Abundant LacZ activity in the absence of Cre expression in the normal and inflamed synovium of adult Col2a1-Cre; ROSA26RLacZ reporter mice

AbstractInterleukin (IL)-11 is a member of the IL-6 family of cytokines and is involved in multiple cellular responses, including tumor development. However, the origin and functions of IL-11-producing (IL-11+) cells are not fully understood. To characterize IL-11+ cells in vivo, we generate Il11 reporter mice. IL-11+ cells appear in the colon in murine tumor and acute colitis models. Il11ra1 or Il11 deletion attenuates the development of colitis-associated colorectal cancer. IL-11+ cells express fibroblast markers and genes associated with cell proliferation and tissue repair. IL-11 induces the activation of colonic fibroblasts and epithelial cells through phosphorylation of STAT3. Human cancer database analysis reveals that the expression of genes enriched in IL-11+ fibroblasts is elevated in human colorectal cancer and correlated with reduced recurrence-free survival. IL-11+ fibroblasts activate both tumor cells and fibroblasts via secretion of IL-11, thereby constituting a feed-forward loop between tumor cells and fibroblasts in the tumor microenvironment.

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Adipocyte death triggers a pro-inflammatory response and induces metabolic activation of resident macrophages

Cell Death and Disease ◽

10.1038/s41419-021-03872-9 ◽

2021 ◽

Vol 12 (6) ◽

Author(s):

Andreas Lindhorst ◽

Nora Raulien ◽

Peter Wieghofer ◽

Jens Eilers ◽

Fabio M. V. Rossi ◽

...

Keyword(s):

Inflammatory Response ◽

Metabolic Activation ◽

Degradation Process ◽

Critical Threshold ◽

Low Grade ◽

Blood Monocytes ◽

Threshold Size ◽

Laser Injury ◽

Reporter Mice

AbstractA chronic low-grade inflammation within adipose tissue (AT) seems to be the link between obesity and some of its associated diseases. One hallmark of this AT inflammation is the accumulation of AT macrophages (ATMs) around dead or dying adipocytes, forming so-called crown-like structures (CLS). To investigate the dynamics of CLS and their direct impact on the activation state of ATMs, we established a laser injury model to deplete individual adipocytes in living AT from double reporter mice (GFP-labeled ATMs and tdTomato-labeled adipocytes). Hence, we were able to detect early ATM-adipocyte interactions by live imaging and to determine a precise timeline for CLS formation after adipocyte death. Further, our data indicate metabolic activation and increased lipid metabolism in ATMs upon forming CLS. Most importantly, adipocyte death, even in lean animals under homeostatic conditions, leads to a locally confined inflammation, which is in sharp contrast to other tissues. We identified cell size as cause for the described pro-inflammatory response, as the size of adipocytes is above a critical threshold size for efferocytosis, a process for anti-inflammatory removal of dead cells during tissue homeostasis. Finally, experiments on parabiotic mice verified that adipocyte death leads to a pro-inflammatory response of resident ATMs in vivo, without significant recruitment of blood monocytes. Our data indicate that adipocyte death triggers a unique degradation process and locally induces a metabolically activated ATM phenotype that is globally observed with obesity.

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Novel, Non–Gene-Destructive Knock-In Reporter Mice Refute the Concept of Monoallelic Gata3 Expression

The Journal of Immunology ◽

10.4049/jimmunol.2000025 ◽

2020 ◽

Vol 204 (9) ◽

pp. 2600-2611

Author(s):

Tata Nageswara Rao ◽

Suresh Kumar ◽

Alex Jose Pulikkottil ◽

Franziska Oliveri ◽

Rudi W. Hendriks ◽

...

Keyword(s):

Reporter Mice ◽

Gata3 Expression

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Knock-In Reporter Mice Demonstrate that DNA Repair by Non-homologous End Joining Declines with Age

PLoS Genetics ◽

10.1371/journal.pgen.1004511 ◽

2014 ◽

Vol 10 (7) ◽

pp. e1004511 ◽

Cited By ~ 50

Author(s):

Amita Vaidya ◽

Zhiyong Mao ◽

Xiao Tian ◽

Brianna Spencer ◽

Andrei Seluanov ◽

...

Keyword(s):

Dna Repair ◽

End Joining ◽

Reporter Mice ◽

Non Homologous End Joining

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Activation of two distinct Sox9-EGFP-expressing intestinal stem cell populations during crypt regeneration after irradiation

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00519.2011 ◽

2012 ◽

Vol 302 (10) ◽

pp. G1111-G1132 ◽

Cited By ~ 97

Author(s):

Laurianne Van Landeghem ◽

M. Agostina Santoro ◽

Adrienne E. Krebs ◽

Amanda T. Mah ◽

Jeffrey J. Dehmer ◽

...

Keyword(s):

Stem Cell ◽

Cell Populations ◽

Intestinal Epithelial ◽

P53 Signaling ◽

Reporter Mice ◽

Radiation Induced ◽

Molecular Phenotypes ◽

Stem Cell Populations ◽

Induced Changes

Recent identification of intestinal epithelial stem cell (ISC) markers and development of ISC reporter mice permit visualization and isolation of regenerating ISCs after radiation to define their functional and molecular phenotypes. Previous studies in uninjured intestine of Sox9-EGFP reporter mice demonstrate that ISCs express low levels of Sox9-EGFP (Sox9-EGFP Low), whereas enteroendocrine cells (EEC) express high levels of Sox9-EGFP (Sox9-EGFP High). We hypothesized that Sox9-EGFP Low ISCs would expand after radiation, exhibit enhanced proliferative capacities, and adopt a distinct gene expression profile associated with rapid proliferation. Sox9-EGFP mice were given 14 Gy abdominal radiation and studied between days 3 and 9 postradiation. Radiation-induced changes in number, growth, and transcriptome of the different Sox9-EGFP cell populations were determined by histology, flow cytometry, in vitro culture assays, and microarray. Microarray confirmed that nonirradiated Sox9-EGFP Low cells are enriched for Lgr5 mRNA and mRNAs enriched in Lgr5-ISCs and identified additional putative ISC markers. Sox9-EGFP High cells were enriched for EEC markers, as well as Bmi1 and Hopx, which are putative markers of quiescent ISCs. Irradiation caused complete crypt loss, followed by expansion and hyperproliferation of Sox9-EGFP Low cells. From nonirradiated intestine, only Sox9-EGFP Low cells exhibited ISC characteristics of forming organoids in culture, whereas during regeneration both Sox9-EGFP Low and High cells formed organoids. Microarray demonstrated that regenerating Sox9-EGFP High cells exhibited transcriptomic changes linked to p53-signaling and ISC-like functions including DNA repair and reduced oxidative metabolism. These findings support a model in which Sox9-EGFP Low cells represent active ISCs, Sox9-EGFP High cells contain radiation-activatable cells with ISC characteristics, and both participate in crypt regeneration.

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Abstract 016: Cells Programmed for the Renin Phenotype Contribute to Vascular Pathology in Renin Deficient Mice

Hypertension ◽

10.1161/hyp.68.suppl_1.016 ◽

2016 ◽

Vol 68 (suppl_1) ◽

Author(s):

Masafumi Oka ◽

Silvia Medrano ◽

Maria Luisa S Sequeira-Lopez ◽

R A Gomez

Keyword(s):

Arterial Wall ◽

Fluorescent Protein ◽

Yellow Fluorescent Protein ◽

Renin Angiotensin System ◽

Arterial Disease ◽

Vascular Pathology ◽

Wall Thickening ◽

Knock Out ◽

Reporter Mice ◽

Specific Proteins

Deletions of the renin-angiotensin system genes or pharmacological inhibition in early life result in a distinctive renal pathology: concentric and disorganized intra-renal arteriolar thickening. The origin and distribution of the cells contributing to the arterial disease are not known. Because the arteriolar thickening disappears with ablation of renin cells, we hypothesized that renin cell precursors contribute to the arterial pathology. To reveal the origin and distribution of the cells responsible for the arterial thickening we generated several mouse lines for fate tracing and also stained for cell identity specific proteins. Kidneys from Ren1c-/- (n=6) and Ren1c+/- (n=6) mice were immunostained for renin, αSMA and PECAM1. Arterial wall thickness was measured using a light microscope and the Leica MM AF ® version1.5 software. Renin cells (unable to produce renin because of the knock out) were identified using Ren1c-/-; Ren1c-YFP mice, where the yellow fluorescent protein is expressed by the Ren1c-YFP transgene designed to label all cells with an active renin promoter. In addition, we tracked the expression and distribution of aldo-keto reductase 1b7, AKR1b7, which mark cells programmed for the renin phenotype even when renin is absent. As expected, Ren1c-/- kidneys showed no renin and thicker intra-renal arteries (Arterioles: Ren1c+/- , 8.26 ± 2.5 μm vs. Ren1c-/- , 14.3 ± 3.8 μm, P<0.0001 , larger arteries: Ren1c+/- , 29.2 ± 11.1 μm vs. Ren1c-/- , 42.1 ± 11.1 μm, P<0.0001 ) AKR1b7+ and YFP+ cells were retained and observed throughout the renal arterioles. To investigate the fate and distribution of cells from the renin lineage, we used Ren1c-Cre and R26R.LacZ or mT/mG reporter mice (6 knock out and 6 control mice per strain). Cells from the renin lineage surrounded arterioles and persisted within larger arterial walls whereas PECAM1+ endothelial cells did not contribute to the arterial wall thickening. In control mice, renin cells were confined to the juxtaglomerular area. We conclude that precursor cells programmed for the renin phenotype maintain their molecular program and together with vascular smooth muscle cells contribute to nephro-vascular disease.

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