Med13 and Med13L: Critical redundant players in basal cardiac function and gene expression

Kayla M. Henry; Richard N. Gardner; Alexis M. Oppman; Nastaran Daneshgar; Mariela Rosales; Ines Martins; Kedryn K. Baskin; Chad E. Grueter

doi:10.1016/j.jmccpl.2025.100481

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Med13 and Med13L: Critical redundant players in basal cardiac function and gene expression

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Med13 and Med13L: Critical redundant players in basal cardiac function and gene expression

Kayla M. Henry, Richard N. Gardner, Alexis M. Oppman, Nastaran Daneshgar, Mariela Rosales, Ines Martins, Kedryn K. Baskin and Chad E. Grueter

Journal of Molecular and Cellular Cardiology Plus (Online), Vol.13, 100481

09/2025

DOI: 10.1016/j.jmccpl.2025.100481

PMCID: PMC12451381

PMID: 40989238

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Abstract

Background Previous studies have linked mutations in the Mediator complex, specifically Mediator 13 (Med13) and Mediator 13-like (Med13L), with both congenital heart defects and cardiovascular diseases. Med13 and Med13L are mutually exclusive paralogs within the kinase submodule of the Mediator complex that have been shown to have partially redundant functions in embryonic development and transcription, but their combined roles have not been investigated in the adult heart. We investigated the critical yet redundant roles of Med13 and Med13L in adult murine cardiomyocytes for basal cardiac function. Methods We generated an inducible Med13 and Med13L cardiomyocyte-specific knockout mouse model to investigate Med13 and Med13L regulation of cardiac function and transcription. We performed RNAseq on mice four weeks after the start of tamoxifen to identify changes in gene expression. Differentially expressed genes were compared across cardiac knockouts of Med13/13L, Med13, Med12, Med1, and Med30 elucidating similar mechanisms of cardiac dysfunction. Results Med13/13L knockout resulted in decreased cardiac function leading to lethal heart failure in a median timeframe of 6 weeks from the start of tamoxifen. There is significant gene dysregulation after Med13/13L knockout with similar gene dysregulation of fibrotic pathways and calcium handling across Mediator cardiac knockouts. Conclusions Med13 and Med13L function partially redundantly within the heart to maintain basal cardiac function and transcription, as well as redundancies within cardiac phenotypes related to mediator complex disruptions.

Med13

Med13L

Cardiac function

Heart failure

Mediator complex

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Title: Subtitle: Med13 and Med13L: Critical redundant players in basal cardiac function and gene expression
Creators: Kayla M. Henry - University of Iowa
Richard N. Gardner
Alexis M. Oppman
Nastaran Daneshgar - University of Iowa
Mariela Rosales - University of Iowa
Ines Martins
Kedryn K. Baskin - The Ohio State University Wexner Medical Center
Chad E. Grueter
Resource Type: Journal article
Publication Details: Journal of Molecular and Cellular Cardiology Plus (Online), Vol.13, 100481
DOI: 10.1016/j.jmccpl.2025.100481
PMID: 40989238
PMCID: PMC12451381
NLM abbreviation: J Mol Cell Cardiol Plus
ISSN: 2772-9761
eISSN: 2772-9761
Publisher: ELSEVIER
Grant note: NIH/NHLBI: 1 R01HL168044 NIH Predoctoral Training Grant: T32GM145441 MED13L Foundation: R01HL166520
This work was funded by the NIH/NHLBI 1 R01HL168044 (CEG) , NIH Predoctoral Training Grant T32GM145441 (KMH) , the MED13L Foundation, and R01HL166520 (KKB) .
Language: English
Electronic publication date: 08/31/2025
Date published: 09/2025
Academic Unit: Neurology; Cardiovascular Medicine; Craniofacial Anomalies Research Center; Internal Medicine
Record Identifier: 9984958293202771

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