Evidence map›Paper›PMID 39185211›Full record

ArticlebioRxiv : the preprint server for biology2025

Reconciling the effects of PMS2 in different repeat expansion disease models supports a common therapeutic strategy.

Diego Antonio Jimenez, Carson J Miller, Alexandra Walker, Kusala Anupindi, Bruce E Hayward, Hernan A Lorenzi, Karen Usdin, Xiaonan Zhao

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors.

Diego Antonio JimenezSection on Gene Structure and Disease, Laboratory of Cell and Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892.
Carson J MillerSection on Gene Structure and Disease, Laboratory of Cell and Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892.ORCID 0000-0001-5459-7015
Alexandra WalkerSection on Gene Structure and Disease, Laboratory of Cell and Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892.
Kusala AnupindiSection on Gene Structure and Disease, Laboratory of Cell and Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892.ORCID 0009-0004-0474-5330
Bruce E HaywardSection on Gene Structure and Disease, Laboratory of Cell and Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892.
Hernan A LorenziThe TriLabs Bioinformatics Group, Laboratory of Biochemistry and Genetics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892.ORCID 0000-0003-0910-7894
Karen UsdinSection on Gene Structure and Disease, Laboratory of Cell and Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892.ORCID 0000-0003-3295-0740
Xiaonan ZhaoSection on Gene Structure and Disease, Laboratory of Cell and Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892.ORCID 0000-0001-7281-3914

Funding

Understanding the mutational mechanism responsible for the Repeat Expansion DiseasesZIADK057808 · NIDDK · NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES · PI USDIN, KAREN P. · 2009 to 2025
$14.1M
Mechanism of repeat expansion in Fragile X syndromeZ01DK057808 · NIDDK · NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES · PI USDIN, KAREN P. · 2007 to 2008
$570k
Intramural NIH HHS Z01 DK057808
6 · The paper itself

Abstract

Expansion of a disease-specific tandem repeat is responsible for >45 Repeat Expansion Diseases (REDs). The expansion mutation in each of these diseases has different pathological consequences and most are currently incurable. If the underlying mechanism of mutation is shared, a strategy that slows repeat expansion in one RED may be applicable to multiple REDs. However, the fact that PMS2, a component of the MutLα mismatch repair complex, promotes expansion in some models and protects against it in others, suggests that the expansion mechanisms may differ. We show here using mouse models of two REDs caused by different repeats that the seemingly paradoxical effects of PMS2 do not reflect different expansion mechanisms but rather cell-type and dosage effects in different tissues. This differential effect is recapitulated in mouse embryonic stem cells with inducible PMS2 expression: PMS2 promotes expansion at low concentrations, an effect that requires a functional nuclease domain; while at higher concentrations it protects against expansion. The apparent paradoxical behavior of PMS2 can be resolved in a model based on the different

Indexed as

fragile X-related disordersHuntington’s diseasemicrosatellite instabilityMutLαMutLγ

Identifiers

PMID39185211
PMCPMC11343130

What OpenQuestion holds

Textmetadata
LicenceCC0
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.