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Heart and extra-embryonic mesodermal defects in mouse embryos lacking the bHLH transcription factor Hand1
A B Firulli1, D G McFadden, Q Lin
1Department of Molecular Biology, The University of Texas Southwestern Medical Center at Dallas, 75235-9148, USA.
Nature Genetics
|March 21, 1998
Summary
The basic helix-loop-helix transcription factor Hand1 is crucial for embryonic development. Hand1 null mutations in mice lead to severe yolk sac and heart defects, causing embryonic lethality.
Area of Science:
- Developmental Biology
- Genetics
- Molecular Biology
Background:
- Basic helix-loop-helix (bHLH) transcription factors Hand1 and Hand2 are vital during embryogenesis.
- Hand2 is essential for right ventricle and aortic arch artery formation.
- Hand1 expression is noted in extraembryonic membranes, while Hand2 is found in the deciduum.
Purpose of the Study:
- To investigate the role of Hand1 in mouse embryogenesis by creating a germline mutation.
- To analyze the developmental consequences of Hand1 deficiency.
Main Methods:
- Generation of a germline mutation in the mouse Hand1 gene.
- Replacement of the first coding exon with a beta-galactosidase reporter gene.
- Analysis of Hand1 null allele embryos.
Main Results:
- Homozygous Hand1 null embryos exhibited embryonic lethality between days 8.5 and 9.5.
- Significant yolk sac abnormalities were observed, indicating a deficiency in extraembryonic mesoderm.
- Heart development was severely perturbed, failing to progress beyond the cardiac-looping stage.
Conclusions:
- Hand1 plays a critical role in extraembryonic mesoderm development.
- Hand1 is essential for normal heart development during embryogenesis.

