Evidence map›Paper›PMID 40960281›Full record

ArticleDevelopment (Cambridge, England)2025

Hand1 gene replacement with Hand2 reveals overlap in function with unique occurrence of omphalocele and heart defects.

Beth A Firulli, Chloe A Ferguson, Corrie de Gier-de Vries, Ram Podicheti, Douglas B Rusch, Vincent M Christoffels, Michael Rubart-von der Lohe, Anthony B Firulli

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Development (Cambridge, England), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Genetic loci responsible for atrioventricular block in children.Frontiers in cell and developmental biology · 2026
    Review
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

8 authors.

Beth A FirulliHerman B Wells Center for Pediatric Research Department of Pediatrics, Anatomy, Biochemistry, and Medical and Molecular Genetics, Indiana University School of Medicine, 1044 W. Walnut Street, Indianapolis, IN 46202-5225, USA.
Chloe A FergusonHerman B Wells Center for Pediatric Research Department of Pediatrics, Anatomy, Biochemistry, and Medical and Molecular Genetics, Indiana University School of Medicine, 1044 W. Walnut Street, Indianapolis, IN 46202-5225, USA.
Corrie de Gier-de VriesDepartment of Medical Biology, Academic Medical Center, University of Amsterdam, 22660, 1100 DD Amsterdam, The Netherlands.
Ram PodichetiCenter for Genomics and Bioinformatics, Indiana University, Bloomington, IN 47405, USA.
Douglas B RuschCenter for Genomics and Bioinformatics, Indiana University, Bloomington, IN 47405, USA.
Vincent M ChristoffelsDepartment of Medical Biology, Academic Medical Center, University of Amsterdam, 22660, 1100 DD Amsterdam, The Netherlands.
Michael Rubart-von der LoheHerman B Wells Center for Pediatric Research Department of Pediatrics, Anatomy, Biochemistry, and Medical and Molecular Genetics, Indiana University School of Medicine, 1044 W. Walnut Street, Indianapolis, IN 46202-5225, USA.
Anthony B FirulliHerman B Wells Center for Pediatric Research Department of Pediatrics, Anatomy, Biochemistry, and Medical and Molecular Genetics, Indiana University School of Medicine, 1044 W. Walnut Street, Indianapolis, IN 46202-5225, USA.ORCID 0000-0001-6687-8949

Funding

Transcriptional regulation of cardiac morphogenesisP01HL134599 · NHLBI · INDIANA UNIVERSITY INDIANAPOLIS · PI Anthony B. Firulli · 2017 to 2026
$25.7M
Indiana University-Purdue University IndianapolisNHLBI NIH HHS 1R01HL120920NHLBI NIH HHS 2P01HL134599NHLBI NIH HHS P01 HL134599
6 · The paper itself

Abstract

The bHLH transcription factors HAND1 and HAND2 are expressed in partially overlapping patterns during development. Studies have established evidence for significant functional redundancy between HAND1 and HAND2. To test redundancy fully, we engineered a Hand1 allele in which we directly replaced the Hand1 exons and intron with those of Hand2. The results show that 2% of Hand1Hand2/Hand2 mice are viable and fertile. The remaining Hand1Hand2/Hand2 embryos exhibit neonatal lethality due to omphalocele accompanied by ventricular septal defects and conduction anomalies. Omphalocele can occur due to altered gut rotation. Our transcriptomic expression analysis reveals that established gene expression patterns associated with normal gut rotation are compromised. Interrogation of cardiac function in surviving Hand1Hand2/Hand2 mice reveals QRS abnormalities and cardiac morphogenic defects. These data support previous findings that HAND factors exhibit extensive functional overlap but also reveals that HAND1 protein has unique functions within the Hand1 expression domain and is required for normal embryonic development.

Indexed as

Basic Helix-Loop-Helix ProteinsHeart Defects, CongenitalHernia, UmbilicalAnimalsFemaleGene Expression Regulation, DevelopmentalMiceBasic Helix-Loop-Helix ProteinsHand1 protein, mouseHand2 protein, mouseGene replacementGut malrotationHAND factorHeart developmentMouseOmphaloceleTranscriptomics

Identifiers

PMID40960281
PMCPMC12587295

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.