Heterozygous Med13l mice recapitulate a developmental growth delay and craniofacial anomalies seen in MED13L syndrome

Anna K Leinheiser; Timothy T Nguyen; Kayla M Henry; Mariela Rosales; Eric Van Otterloo; Chad E Grueter

doi:10.1002/dvdy.70079

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Heterozygous Med13l mice recapitulate a developmental growth delay and craniofacial anomalies seen in MED13L syndrome

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Heterozygous Med13l mice recapitulate a developmental growth delay and craniofacial anomalies seen in MED13L syndrome

Anna K Leinheiser, Timothy T Nguyen, Kayla M Henry, Mariela Rosales, Eric Van Otterloo and Chad E Grueter

Developmental dynamics

09/08/2025

DOI: 10.1002/dvdy.70079

PMCID: PMC13052522

PMID: 40919805

Appears in UI Libraries Support Open Access

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Abstract

Gene transcription is crucial for embryo and postnatal development and is regulated by the Mediator complex. Mediator is comprised of four submodules, including the kinase submodule (CKM). The CKM consists of MED13, MED12, CDK8, and CCNC. In mammals, there are paralogs for CKM components, including MED13L, MED12L, and CDK19. Neurological disorders have been associated with mutations in CKM genes including MED13L syndrome. MED13L syndrome is generally characterized as a haploinsufficiency of MED13L with a broad phenotypic response due in part to a wide range of de novo mutations. We developed a Med13l heterozygous (HET) mouse model with an exon 11 deletion to evaluate whether Med13l HET mice are a viable research tool to study human phenotypes. We characterized our mouse model using growth, cardiovascular, and skeletal readouts. We observed Med13l HET mice are smaller than wildtype (WT) littermates, and over 60% of them exhibited one of two craniofacial anomalies: a pug snout with midface hypoplasia or a crooked snout. We also observed discontinuous squamosal sutures in a subset of our Med13l HETs. Med13l HET mice recapitulate MED13L syndrome phenotypes including a developmental growth delay and craniofacial anomalies. Med13l HET mice represent a novel research tool for MED13L syndrome.

haploinsufficiency

mouse model

developmental growth delay

neural crest

MED13L syndrome

craniofacial anomalies

mediator

UIOWA OA Agreement

Details

Title: Subtitle: Heterozygous Med13l mice recapitulate a developmental growth delay and craniofacial anomalies seen in MED13L syndrome
Creators: Anna K Leinheiser - University of Iowa
Timothy T Nguyen - University of Iowa
Kayla M Henry - University of Iowa
Mariela Rosales - University of Iowa
Eric Van Otterloo - University of Iowa
Chad E Grueter - University of Iowa
Resource Type: Journal article
Publication Details: Developmental dynamics
DOI: 10.1002/dvdy.70079
PMID: 40919805
PMCID: PMC13052522
NLM abbreviation: Dev Dyn
ISSN: 1058-8388
eISSN: 1097-0177
Publisher: Wiley
Grant note: T32GM145441 / NIGMS NIH HHS MED13L Foundation T32DK112751 / Division of Diabetes, Endocrinology, and Metabolic Diseases University of Iowa College of Dentistry 1R01HL168044 / NHLBI NIH HHS R01 HL168044 / NHLBI NIH HHS F31DE032881 / NIDCR NIH HHS R01DE033009 / NIDCR NIH HHS
Language: English
Electronic publication date: 09/08/2025
Academic Unit: Anatomy and Cell Biology; Cardiovascular Medicine; Craniofacial Anomalies Research Center; Dental Research; Periodontics; Internal Medicine
Record Identifier: 9984962541402771

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