Evidence map›Paper›PMID 33122788›Full record

ArticleScientific reports2020

Generation of a Matrix Gla (Mgp) floxed mouse, followed by conditional knockout, uncovers a new Mgp function in the eye.

Teresa Borrás, Dale O Cowley, Priyadarsini Asokan, Kumar Pandya

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.6field-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

5 citing papers in PubMed, 10 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Viral Vector-Induced Ocular Hypertension in Mice.Methods in molecular biology (Clifton, N.J.) · 2023
    Article
  5. Article
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

4 authors at 1 institution in 1 country.

Teresa BorrásDepartment of Ophthalmology, University of North Carolina School of Medicine, 4109C Neuroscience Research Building CB 7041, 115 Mason Farm Road, Chapel Hill, NC, 27599-7041, USA. tborras@med.unc.edu.
Dale O CowleyAnimal Models Core, University of North Carolina, Chapel Hill, NC, USA.
Priyadarsini AsokanDepartment of Ophthalmology, University of North Carolina School of Medicine, 4109C Neuroscience Research Building CB 7041, 115 Mason Farm Road, Chapel Hill, NC, 27599-7041, USA.
Kumar PandyaAnimal Models Core, University of North Carolina, Chapel Hill, NC, USA.
University of North Carolina at Chapel Hill · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4M
Virology Research Program (Program 4)P30CA016086 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Deborah F. Tate · 1985 to 2026
$201.5M
REGULATION OF OUTFLOW FACILITY BY GENE TRANSFERR01EY011906 · NEI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BORRAS, TERESA · 1997 to 2016
$5.6M
Targeting calcification/ stiffness in glaucoma with Matrix GlaR01EY026220 · NEI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI MEI, HUA · 2016 to 2020
$1.9M
Mechanisms of Formation of Pseudoexfoliation Material on Human Surgical Lens CapsulesR21EY030608 · NEI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI MEI, HUA · 2019 to 2020
$428k
NCI NIH HHS P30 CA008748NCI NIH HHS P30 CA016086NEI NIH HHS R01 EY011906NEI NIH HHS R01 EY026220NEI NIH HHS R21 EY030608NIH HHS EY026220 (TB)NIH HHS EY030608 (TB)NIH HHS EY11906 (TB)NIH HHS P30 CA016086 (DOC)
6 · The paper itself

Abstract

The ability to ablate a gene in a given tissue by generating a conditional knockout (cKO) is crucial for determining its function in the targeted tissue. Such tissue-specific ablation is even more critical when the gene's conventional knockout (KO) is lethal, which precludes studying the consequences of its deletion in other tissues. Therefore, here we describe a successful strategy that generated a Matrix Gla floxed mouse (Mgp.floxed) by the CRISPR/Cas9 system, that subsequently allowed the generation of cKOs by local viral delivery of the Cre-recombinase enzyme. MGP is a well-established inhibitor of calcification gene, highly expressed in arteries' smooth muscle cells and chondrocytes. MGP is also one of the most abundant genes in the trabecular meshwork, the eye tissue responsible for maintenance of intraocular pressure (IOP) and development of Glaucoma. Our strategy entailed one-step injection of two gRNAs, Cas9 protein and a long-single-stranded-circular DNA donor vector (lsscDNA, 6.7 kb) containing two loxP sites in cis and 900-700 bp 5'/3' homology arms. Ocular intracameral injection of Mgp.floxed mice with a Cre-adenovirus, led to an Mgp.TMcKO mouse which developed elevated IOP. Our study discovered a new role for the Mgp gene as a keeper of physiological IOP in the eye.

Indexed as

Intraocular PressureAnimalsBase SequenceCalcium-Binding ProteinsExtracellular Matrix ProteinsEyeFemaleGlaucomaIntegrasesMatrix Gla ProteinMiceMice, KnockoutRNA, Guide, CRISPR-Cas SystemsTrabecular MeshworkCalcium-Binding ProteinsCre recombinaseExtracellular Matrix ProteinsIntegrasesMatrix Gla ProteinRNA, Guide, CRISPR-Cas Systems

Identifiers

PMID33122788
PMCPMC7596545
OpenAlexW3096047298

What OpenQuestion holds

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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.