Evidence map›Paper›PMID 26450994›Full record

ArticleDiabetes2016

A SNP in the Immunoregulatory Molecule CTLA-4 Controls mRNA Splicing In Vivo but Does Not Alter Diabetes Susceptibility in the NOD Mouse.

Fabian Jakubczik, Ken Jones, Jennifer Nichols, William Mansfield, Anne Cooke, Nick Holmes

Open access · bronzeAbstract read
In one paragraph

Article in Diabetes, 2016. 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
1.2field-weighted citation impact, top 17% 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, 8 citations in OpenAlex.

  1. Relationship of PSC to embryos: Extending and refining capture of PSC lines from mammalian embryos.BioEssays : news and reviews in molecular, cellular and developmental biology · 2024
    Review
  2. Article
  3. Using GWAS to identify novel therapeutic targets for osteoporosis.Translational research : the journal of laboratory and clinical medicine · 2017
    Review
  4. 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

6 authors at 2 institutions in 1 country.

Fabian JakubczikDepartment of Pathology, University of Cambridge, Cambridge, U.K.
Ken JonesWellcome Trust Centre for Stem Cell Research, University of Cambridge, Cambridge, U.K. Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, U.K.
Jennifer NicholsWellcome Trust Centre for Stem Cell Research, University of Cambridge, Cambridge, U.K. Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, U.K.ORCID 0000-0002-8650-1388
William MansfieldWellcome Trust Centre for Stem Cell Research, University of Cambridge, Cambridge, U.K.
Anne CookeDepartment of Pathology, University of Cambridge, Cambridge, U.K.ORCID 0000-0003-3327-6081
Nick HolmesDepartment of Pathology, University of Cambridge, Cambridge, U.K. nh106@cam.ac.uk.
University of Cambridge · GBWellcome/MRC Cambridge Stem Cell Institute · GB

Funding

Wellcome Trust 086822Wellcome Trust 97922
6 · The paper itself

Abstract

CTLA-4 is a critical "checkpoint" regulator in autoimmunity. Variation in CTLA-4 isoform expression has been linked to type 1 diabetes development in human and NOD mouse studies. In the NOD mouse, a causative link between increased expression of the minor isoform ligand-independent CTLA-4 and a reduction in diabetes has become widely accepted. Altered splicing of CTLA-4 has been attributed to a single nucleotide polymorphism (SNP) in Ctla4 exon2 (e2_77A/G). To investigate this link, we have used NOD embryonic stem (ES) cells to generate a novel NOD transgenic line with the 77A/G SNP. This strain phenocopies the increase in splicing toward the liCTLA4 isoform seen in B10 Idd5.1 mice. Crucially, the SNP does not alter the spontaneous incidence of diabetes, the incidence of cyclophosphamide-induced diabetes, or the activation of diabetogenic T-cell receptor transgenic CD4(+) T cells after adoptive transfer. Our results show that one or more of the many other linked genetic variants between the B10 and NOD genome are required for the diabetes protection conferred by Idd5.1. With the NOD mouse model closely mimicking the human disease, our data demonstrate that knock-in transgenic mice on the NOD background can test causative mutations relevant in human diabetes.

Indexed as

Adoptive TransferAnimalsAutoimmunityCD4-Positive T-LymphocytesCTLA-4 AntigenDiabetes Mellitus, Type 1Gene Knock-In TechniquesGenetic Predisposition to DiseaseMiceMice, Inbred NODMice, TransgenicMouse Embryonic Stem CellsPolymorphism, Single NucleotideProtein IsoformsRNA, MessengerRNA SplicingCTLA-4 AntigenCtla4 protein, mouseProtein IsoformsRNA, Messenger

Identifiers

PMID26450994
PMCPMC4693968
OpenAlexW2173546767

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.