Constitutive overexpression of Norrin activates Wnt/β-catenin and endothelin-2 signaling to protect photoreceptors from light damage

Braunger, Barbara M.; Ohlmann, Andreas; Koch, Marcus A.; Tanimoto, Naoyuki; Volz, Cornelia; Yang, Ying; Bösl, Michael R.; Cvekl, Aleš; Jägle, Herbert; Seeliger, Mathias W.; Tamm, Ernst R.

doi:10.1016/j.nbd.2012.09.008

Cited by 53 publications

(59 citation statements)

References 29 publications

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“…Genotypes were screened by isolating genomic DNA from tail biopsies and testing for transgenic sequences by PCR as described previously [18]. For detection of Cre primer sequences were 5'-ATG CTT CTG TCC GTT TGC CG-3' (sense) and 5'-CCT GTT TTG CAC GTT CAC CG-3' (antisense) and for lacZ genotyping the primer sequences were 5'-ATC CTC TGC ATG GTC AGG TC-3' (sense) and 5'-CGT GGC CTG ATT CAT TCC-3' (antisense).…”

Section: Pcr Analyses For Genotypingmentioning

confidence: 99%

“…For detection of Cre primer sequences were 5'-ATG CTT CTG TCC GTT TGC CG-3' (sense) and 5'-CCT GTT TTG CAC GTT CAC CG-3' (antisense) and for lacZ genotyping the primer sequences were 5'-ATC CTC TGC ATG GTC AGG TC-3' (sense) and 5'-CGT GGC CTG ATT CAT TCC-3' (antisense). Lmop-Cre)/R26R and R26R mice following a previously published protocol [18]. Paraffin sections (6 µm thick) were analyzed using an Axio Imager Z1 light microscope (Carl Zeiss Microscopy GmbH, Jena, Germany) and the appropriate Axiovision software 4.8 (Carl Zeiss Microscopy GmbH, Jena, Germany).…”

Section: Pcr Analyses For Genotypingmentioning

confidence: 99%

“…The sections were always stretching through the optic nerve head to ensure comparable conditions between the individual sections. Subsequently, ONL or INL thickness was measured at these measure points and the means± SEM of the ONL or INL thickness were plotted in a spider diagram as described in [18,22].…”

Section: Microscopy and Morphometrymentioning

confidence: 99%

“…To experimentally induce the apoptosis of photoreceptor cells [25][26][27], six to seven weeks old albino mice that were homozygous for the L450 variant of RPE65 [13] were transferred to cyclic dim light (<100 lux) for 5 d followed by a a dark-adapting period of 12 h. Mice were then placed in reflective cages and exposed to diffuse cool, white fluorescent light coming from the top of the cage with an intensity of 5000 lux for 30 min. Average intensity was measured on the cage floor (5000 lux).…”

Section: Light Damagementioning

confidence: 99%

“…Paraffin sections were treated following manufacturers' instructions and protocols reported previously [18]. For quantitative analysis, the number of TUNEL-positive nuclei in sagittal sections throughout the entire retina was counted using the ImageJ software program and normalized to the area of the ONL [18,28].…”

Section: Terminal Deoxynucleotidyl Transferase-mediated Dutp Nick Endmentioning

confidence: 99%

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Cre recombinase expression or topical tamoxifen treatment do not affect retinal structure and function, neuronal vulnerability or glial reactivity in the mouse eye

et al. 2016

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Braunger, B. M. (2016). Cre recombinase expression or topical tamoxifen treatment do not affect retinal structure and function, neuronal vulnerability or glial reactivity in the mouse eye. Neuroscience. DOI: 10.1016DOI: 10. /j.neuroscience.2016 Citing this paper Please note that where the full-text provided on King's Research Portal is the Author Accepted Manuscript or Post-Print version this may differ from the final Published version. If citing, it is advised that you check and use the publisher's definitive version for pagination, volume/issue, and date of publication details. And where the final published version is provided on the Research Portal, if citing you are again advised to check the publisher's website for any subsequent corrections. General rightsCopyright and moral rights for the publications made accessible in the Research Portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognize and abide by the legal requirements associated with these rights.•Users may download and print one copy of any publication from the Research Portal for the purpose of private study or research.•You may not further distribute the material or use it for any profit-making activity or commercial gain •You may freely distribute the URL identifying the publication in the Research Portal Take down policy If you believe that this document breaches copyright please contact librarypure@kcl.ac.uk providing details, and we will remove access to the work immediately and investigate your claim. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. analyses. Furthermore, the influence of Cre recombinase or topical tamoxifen exposure on neuronal vulnerability was studied by using light damage as a model for photoreceptor degeneration. Taken together, neither the expression of Cre, nor topical tamoxifen treatment caused detectable changes in retinal structure and function, the expression profiles of investigated molecular markers, glial reactivity and photoreceptor vulnerability. We conclude that the Cre-loxP system and its induction through tamoxifen is a safe and reliable method to delete desired target genes in the neural retina.

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Section: Pcr Analyses For Genotypingmentioning

confidence: 99%

Section: Pcr Analyses For Genotypingmentioning

confidence: 99%

Section: Microscopy and Morphometrymentioning

confidence: 99%

Section: Light Damagementioning

confidence: 99%

Section: Terminal Deoxynucleotidyl Transferase-mediated Dutp Nick Endmentioning

confidence: 99%

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Cre recombinase expression or topical tamoxifen treatment do not affect retinal structure and function, neuronal vulnerability or glial reactivity in the mouse eye

et al. 2016

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Generation and characterization of an endothelin‐2 iCre mouse

Cacioppo

Koo

Lin

et al. 2015

Genesis

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A novel transgenic mouse line that expresses codon-improved Cre recombinase (iCre) under regulation of the Endothelin-2 gene (edn2) promoter was developed for the conditional deletion of genes in Endothelin-2 lineage cells and for the spatial and temporal localization of Endothelin-2 expression. Endothelin-2 (EDN2, ET-2, previously VIC) is a transcriptionally regulated 21 amino acid peptide implicated in vascular homeostasis, and more recently in female reproduction, gastrointestinal function, immunology, and cancer pathogenesis that acts through membrane receptors and G-protein signaling. A cassette (edn2-iCre) was constructed that contained iCre, a polyadenylation sequence, and a neomycin selection marker in front of the endogenous start codon of the edn2 gene in a mouse genome BAC clone. The cassette was introduced into the C57BL/6 genome by pronuclear injection, and two lines of edn2-iCre positive mice were produced. The edn2-iCre mice were bred with ROSA26-lacZ and Ai9 reporter mice to visualize areas of functional iCre expression. Strong expression was seen in the periovulatory ovary, stomach and small intestine, and colon. Uniquely, we report punctate expression in the corneal epithelium, the liver, the lung, the pituitary, the uterus, and the heart. In the embryo, expression is localized in developing hair follicles and the dermis. Therefore, edn2-iCre mice will serve as a novel line for conditional gene deletion in these tissues.

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Faim knockout leads to gliosis and late‐onset neurodegeneration of photoreceptors in the mouse retina

Sirés

Turch-Anguera

Bogdanov

et al. 2021

J of Neuroscience Research

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Fas Apoptotic Inhibitory Molecule protein (FAIM) is a death receptor antagonist and an apoptosis regulator. It encodes two isoforms, namely FAIM-S (short) and FAIM-L (long), both with significant neuronal functions. FAIM-S, which is ubiquitously expressed, is involved in neurite outgrowth. In contrast, FAIM-L is expressed only in neurons and it protects them from cell death. Interestingly, FAIM-L is downregulated in patients and mouse models of Alzheimer's disease before the onset of neurodegeneration, and Faim transcript levels are decreased in mouse models of retinal degeneration. However, few studies have addressed the role of FAIM in the central nervous system, yet alone the retina. The retina is a highly specialized tissue, and its degeneration has proved to precede pathological mechanisms of neurodegenerative diseases. Here we describe that Faim depletion in mice damages the retina persistently and leads to late-onset photoreceptor death in older mice. Immunohistochemical analyses showed that Faim knockout (Faim −/− ) mice present ubiquitinated aggregates throughout the retina from early ages. Moreover, retinal cells released stress signals that can signal to Müller cells, as shown by immunofluorescence and qRT-PCR.Müller cells monitor retinal homeostasis and trigger a gliotic response in Faim −/− mice that becomes pathogenic when sustained. In this regard, we observed pronounced vascular leakage at later ages, which may be caused by persistent inflammation.These results suggest that FAIM is an important player in the maintenance of retinal homeostasis, and they support the premise that FAIM is a plausible early marker for late photoreceptor and neuronal degeneration.

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Constitutive overexpression of Norrin activates Wnt/β-catenin and endothelin-2 signaling to protect photoreceptors from light damage

Cited by 53 publications

References 29 publications

Cre recombinase expression or topical tamoxifen treatment do not affect retinal structure and function, neuronal vulnerability or glial reactivity in the mouse eye

Cre recombinase expression or topical tamoxifen treatment do not affect retinal structure and function, neuronal vulnerability or glial reactivity in the mouse eye

Generation and characterization of an endothelin‐2 iCre mouse

Faim knockout leads to gliosis and late‐onset neurodegeneration of photoreceptors in the mouse retina

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