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The RBPMS^{CreERT2-tdTomato} mouse line for studying retinal and vascular relevant diseases.

ABSTRACT: RNA-binding protein with multiple splicing (RBPMS) plays a crucial role in cardiac mesoderm specification and cardiovascular development, as well as being a typical marker for whole retinal ganglion cells (RGCs). However, there is a lack of animal models to spatiotemporally trace the location and function of RBPMS-expressing cells in vivo. In this study, we develop a tamoxifen-inducible RBPMS-tdTomato reporter mouse line to track RBPMS-expressing cells during embryogenesis and adulthood. This mouse line allows us to identify and locate RBPMS-tdTomato-positive cells among various tissues, especially in RGCs and smooth muscle cells, which assist to simulate related retinal degenerative diseases, model and examine choroidal neovascularization non-invasively in vivo. Our results show that the RBPMS^{CreERT2-tdTomato} mouse line is a valuable tool for lineage tracing, disease modeling, drug screening, as well as isolating specific target cells.

SUBMITTER: Li G

PROVIDER: S-EPMC10589894 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature

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The RBPMS<sup>CreERT2-tdTomato</sup> mouse line for studying retinal and vascular relevant diseases.

Li Guilan G Luo Yuanting Y Zhang Qikai Q Chen Wenfei W Lai Kunbei K Liu Yizhi Y Zheng Yingfeng Y

iScience 20231002 11

RNA-binding protein with multiple splicing (RBPMS) plays a crucial role in cardiac mesoderm specification and cardiovascular development, as well as being a typical marker for whole retinal ganglion cells (RGCs). However, there is a lack of animal models to spatiotemporally trace the location and function of RBPMS-expressing cells <i>in vivo</i>. In this study, we develop a tamoxifen-inducible RBPMS-tdTomato reporter mouse line to track RBPMS-expressing cells during embryogenesis and adulthood. ...[more]

PMID: 37867934

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Project description:BackgroundGenetically modified mice are the most useful tools for investigating the gene functions in articular cartilage biology and the pathogenesis of osteoarthritis. The AggrecanCreERT2 mice are one of the most reported mouse lines used for this purpose. The Prg4 (proteoglycan 4) gene encodes the lubricin protein and is expressed selectively in chondrocytes located at the superficial layer of the articular cartilage. While the Prg4GFPCreERT2 knock-in inducible-Cre transgenic mice were generated a while ago, so far, few studies have used this mouse line to perform gene functional studies in cartilage biology.MethodsWe have recently reported that deleting the Fermt2 gene, which encodes the key focal adhesion protein Kindlin-2, in articular chondrocytes by using the AggrecanCreERT2 transgenic mice, results in spontaneous osteoarthritis (OA) lesions, which highly mimics the human OA pathologies. In this study, we have compared the Kindlin-2 deficiency-caused OA phenotypes induced by Prg4GFPCreERT2 with those caused by AggrecanCreERT2 using imaging and histological analyses.ResultsWe find that Kindlin-2 protein is deleted in about 75% of the superficial articular chondrocytes in the tamoxifen (TAM)-treated Prg4GFPCreERt2/+; Fermt2fl/fl mice compared to controls. At 6 months after TAM injections, the OARSI scores of AggrecanCreERT2/+; Fermt2fl/fl and Prg4GFPCreERt2/+; Fermt2fl/fl mice were 5 and 3, respectively. The knee joints histological osteophyte and synovitis scores were also significantly decreased in Prg4GFPCreERT2/+; Fermt2fl/fl mice compared to those in AggrecanCreERT2/+; Fermt2fl/fl mice. Furthermore, magnitudes of upregulation of the extracellular matrix-degrading enzymes Mmp13 and hypertrophic chondrocyte markers Col10a1 and Runx2 were decreased in Prg4GFPCreERT2/+; Fermt2fl/fl versus AggrecanCreERT2/+; Fermt2fl/fl mice. We finally examined the susceptibility of Prg4GFPCreERT2/+; Fermt2fl/fl mouse model to surgically induce OA lesions. The pathological features of OA in the TAM-DMM model exhibited significant enhancement in cartilage erosion, proteoglycan loss, osteophyte, and synovitis and an increase in OARSI score in articular cartilage compared with those in corn-oil DMM mice.ConclusionKindlin-2 loss causes milder OA-like lesions in Prg4GFPCreERT2/+;Fermt2fl/fl than in AggrecanCreERT2/+; Fermt2fl/fl mice. In contrast, Kindlin-2 loss similarly accelerates the destabilization of the medial meniscus-induced OA lesions in both mice.Translational Potential of this Article: Our study demonstrates that Prg4GFPCreERT2 is a useful tool for gene functional study in OA research. This study provides useful information for investigators to choose appropriate Cre mouse lines for their research in cartilage biology.

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The RBPMS^{CreERT2-tdTomato} mouse line for studying retinal and vascular relevant diseases.

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The RBPMS<sup>CreERT2-tdTomato</sup> mouse line for studying retinal and vascular relevant diseases.

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Dataset Information

The RBPMSCreERT2-tdTomato mouse line for studying retinal and vascular relevant diseases.

Publications

The RBPMS<sup>CreERT2-tdTomato</sup> mouse line for studying retinal and vascular relevant diseases.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

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The RBPMS^{CreERT2-tdTomato} mouse line for studying retinal and vascular relevant diseases.