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Updated: Oct 1, 2026
Transuterine Fetal Tracheal Occlusion Model in Mice
Published on: February 5, 2021
Impaired neural tube closure, axial skeleton malformations, and tracheal ring disruption in TRAF4-deficient mice
Catherine H Régnier1, Régis Masson, Valérie Kedinger
1Institut de Génétique et de Biologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique Unité Propre de Recherche 6520/Institut National de la Santé et de la Recherche Médicale Unité 184/Université Louis Pasteur, Illkirch, France.
Abstract:
TRAF4 belongs to the tumor necrosis factor receptor-associated factor (TRAF) family of proteins but, unlike other family members, has not yet been clearly associated to any specific receptor or signaling pathway. To investigate the biological function of TRAF4, we have generated traf4-deficient mice by gene disruption. The traf4 gene mutation is embryonic lethal but with great individual variation, as approximately one third of the homozygous mutant embryos died in utero around embryonic day 14, whereas the others reach adulthood. Surviving mutant mice manifest numerous developmental abnormalities; notably, 100% of homozygous mutant mice suffer respiratory disorder and wheezing caused by tracheal ring disruption. Additional malformations concern mainly the axial skeleton, as the ribs, sternum, tail, and vertebral arches are affected, with various degrees of penetrance. Traf4-deficient mice also exhibit a high incidence of spina bifida, a defect likened to neural tube defects (NTD) that are common congenital malformations in humans. Altogether, our results demonstrate that TRAF4 is required during embryogenesis in key biological processes including the formation of the trachea, the development of the axial skeleton, and the closure of the neural tube. Considering the normal expression pattern of TRAF4 in neural tissues, we can conclude that TRAF4 participates in neurulation in vivo.
Insights
Tumor necrosis factor receptor-associated factor 4 (TRAF4) is essential for embryonic development. Traf4-deficient mice exhibit severe skeletal and respiratory abnormalities, including tracheal ring disruption and spina bifida, highlighting TRAF4
Area of Science:
- Developmental Biology
- Genetics
- Molecular Biology
Background:
- Tumor necrosis factor receptor-associated factor 4 (TRAF4) is a member of the TRAF protein family.
- Unlike other TRAF proteins, TRAF4's specific receptor and signaling pathway associations are not well-defined.
- Understanding TRAF4's function is crucial for comprehending developmental processes.
Purpose of the Study:
- To investigate the biological function of TRAF4 in vivo.
- To determine the role of TRAF4 during embryogenesis and development.
- To identify developmental processes dependent on TRAF4.
Main Methods:
- Generation of traf4-deficient mice using gene disruption.
- Analysis of embryonic lethality and developmental abnormalities in homozygous mutants.
- Phenotypic characterization of surviving mutant mice, including skeletal and respiratory assessments.
Main Results:
- Traf4 gene mutation causes embryonic lethality with variable penetrance.
- Surviving traf4-deficient mice exhibit significant developmental abnormalities.
- Key defects include tracheal ring disruption leading to respiratory disorders, axial skeletal malformations, and a high incidence of spina bifida (neural tube defects).
Conclusions:
- TRAF4 is essential for embryogenesis, particularly in trachea formation, axial skeletal development, and neural tube closure.
- TRAF4 plays a critical role in neurulation.
- These findings establish TRAF4 as a key regulator in multiple embryonic developmental pathways.
