Evidence map›Paper›PMID 25949789›Full record

ArticleSkeletal muscle2015

A reporter mouse for optical imaging of inflammation in mdx muscles.

Leonel Martinez, Natalia V Ermolova, Tomo-O Ishikawa, David B Stout, Harvey R Herschman, Melissa J Spencer

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Skeletal muscle, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.5field-weighted citation impact, top 34% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed, 6 citations in OpenAlex.

  1. Review
  2. Skeletal muscle in health and disease.Disease models & mechanisms · 2020
    Review
  3. Article
  4. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 1 country.

Leonel MartinezDepartment of Neurology and Center for Duchenne Muscular Dystrophy, David Geffen School of Medicine, University of California Los Angeles, 635 Charles Young Dr. South, NRB Room 401, Los Angeles, CA 90095 USA ; Center for Duchenne Muscular Dystrophy at UCLA, Los Angeles, CA 90095 USA.
Natalia V ErmolovaDepartment of Neurology and Center for Duchenne Muscular Dystrophy, David Geffen School of Medicine, University of California Los Angeles, 635 Charles Young Dr. South, NRB Room 401, Los Angeles, CA 90095 USA ; Center for Duchenne Muscular Dystrophy at UCLA, Los Angeles, CA 90095 USA.
Tomo-O IshikawaDepartment of Biological Chemistry, David Geffen School of Medicine, University of California Los Angeles, 341 Boyer Hall, 611 Charles E Young Dr. So, Los Angeles, CA 90095 USA ; Present address: Genomics Business Department, Trans Genic Inc, Kumamoto, 862-0976 Japan.
David B StoutDepartment of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095 USA.
Harvey R HerschmanDepartment of Biological Chemistry, David Geffen School of Medicine, University of California Los Angeles, 341 Boyer Hall, 611 Charles E Young Dr. So, Los Angeles, CA 90095 USA ; Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095 USA ; Molecular Biology Institute, UCLA, Los Angeles, CA 90095 USA.
Melissa J SpencerDepartment of Neurology and Center for Duchenne Muscular Dystrophy, David Geffen School of Medicine, University of California Los Angeles, 635 Charles Young Dr. South, NRB Room 401, Los Angeles, CA 90095 USA ; Center for Duchenne Muscular Dystrophy at UCLA, Los Angeles, CA 90095 USA ; Molecular Biology Institute, UCLA, Los Angeles, CA 90095 USA.
University of California, Los Angeles · USMuscular Dystrophy Association · US

Funding

Training and education CoreU54AR052646 · NIAMS · UNIVERSITY OF PENNSYLVANIA · PI MCNALLY, ELIZABETH M, SWEENEY, H LEE · 2005 to 2020
$24.1M
Pilot and Feasibility ProgramP30DK041301 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ROZENGURT, JUAN ENRIQUE · 1990 to 2019
$18.0M
UCLA Muscular Dystrophy Core CenterP30AR057230 · NIAMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI SPENCER, MELISSA JAN · 2009 to 2018
$6.2M
NIAMS NIH HHS P30 AR057230NIAMS NIH HHS U54 AR052646NIDDK NIH HHS P30 DK041301
6 · The paper itself

Abstract

backgroundDuchenne muscular dystrophy (DMD) is due to mutations in the gene coding for human DMD; DMD is characterized by progressive muscle degeneration, inflammation, fat accumulation, and fibrosis. The mdx mouse model of DMD lacks dystrophin protein and undergoes a predictable disease course. While this model has been a valuable resource for pre-clinical studies aiming to test therapeutic compounds, its utility is compromised by a lack of reliable biochemical tools to quantifiably assay muscle disease. Additionally, there are few non-invasive assays available to researchers for measuring early indicators of disease progression in mdx mice.

methodsMdx mice were crossed to knock-in mice expressing luciferase from the Cox2 promoter. These reporter mice (Cox2 (FLuc/+) DMD (-/-) ) were created to serve as a tool for researchers to evaluate muscle inflammation. Luciferase expression was assayed by immunohistochemistry to insure that it correlated with muscle lesions. The luciferase signal was quantified by optical imaging and luciferase assays to verify that the signal correlated with muscle damage. As proof of principle, Cox2 (FLuc/+) DMD (-/-) mice were also treated with prednisolone to validate that a reduction in luciferase signal correlated with prednisone treatment.

resultsIn this investigation, a novel reporter mouse (Cox2 (FLuc/+) DMD (-/-) mice) was created and validated for non-invasive quantification of muscle inflammation in vivo. In this dystrophic mouse, luciferase is expressed from cyclooxygenase 2 (Cox2) expressing cells and bioluminescence is detected by optical imaging. Bioluminescence is significantly enhanced in damaged muscle of exercised Cox2 (FLuc/+) DMD (-/-) mice compared to non-exercised Cox2 (FLuc/+) DMD (+/+) mice. Moreover, the Cox2 bioluminescent signal is reduced in Cox2 (FLuc/+) DMD (-/-) mice in response to a course of steroid treatment. Reduction in bioluminescence is detectable prior to measurable therapy-elicited improvements in muscle strength, as assessed by traditional means. Biochemical assay of luciferase provides a second means to quantify muscle inflammation.

conclusionsThe Cox2 (FLuc/+) DMD (-/-) mouse is a novel tool to evaluate the therapeutic benefits of drugs intended to target inflammatory aspects of dystrophic pathology. This mouse model will be a useful adjunct to traditional outcome measures in assessing potential therapeutic compounds.

Indexed as

Cox2Cyclooxygenase 2Duchenne muscular dystrophyImagingImmune cellsInflammationLuciferasemdxReporter mouse

Identifiers

PMID25949789
PMCPMC4422315
OpenAlexW2147368000

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.