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Updated: Aug 24, 2026
Transuterine Fetal Tracheal Occlusion Model in Mice
Published on: February 5, 2021
Transient in utero knockout (TIUKO) of C-MYC affects late lung and intestinal development in the mouse
J Craig Cohen1, Donald K Scott, James Miller
1Department of Medicine, LSU School of Medicine, 533 Bolivar St, New Orleans, USA. ccohen@lsuhsc.edu
Background:
Developmentally important genes often result in early lethality in knockout animals. Thus, the direct role of genes in late gestation organogenesis cannot be assessed directly. In utero delivery of transgenes was shown previously to result in high efficiency transfer to pulmonary and intestinal epithelial stem cells. Thus, this technology can be used to evaluate late gestation development.
Results:
In utero gene transfer was used to transfer adenovirus with either an antisense c-myc or a C-MYC ubiquitin targeting protein to knockout out c-myc expression in late gestation lung and intestines. Using either antisense or ubiquitin mediated knockout of C-MYC levels in late gestation resulted in similar effects. Decreased complexity was observed in both intestines and lungs. Stunted growth of villi was evident in the intestines. In the lung, hypoplastic lungs with disrupted aveolarization were observed.
Conclusions:
These data demonstrated that C-MYC was required for cell expansion and complexity in late gestation lung and intestinal development. In addition they demonstrate that transient in utero knockout of proteins may be used to determine the role of developmentally important genes in the lungs and intestines.
Insights
C-MYC is essential for lung and intestinal development during late gestation. In utero gene transfer allows researchers to study the impact of crucial genes on fetal organogenesis.
Area of Science:
- Developmental Biology
- Molecular Genetics
- Genomics
Background:
- Developmentally crucial genes often cause early lethality in knockout models, hindering the study of late gestation organogenesis.
- In utero gene transfer efficiently targets pulmonary and intestinal epithelial stem cells, offering a viable method for late gestation development studies.
Purpose of the Study:
- To investigate the role of C-MYC in late gestation lung and intestinal development using in utero gene transfer.
- To assess the feasibility of transient in utero gene knockout for studying essential developmental genes.
Main Methods:
- Adenovirus-mediated in utero gene transfer was employed to deliver either antisense c-myc or a C-MYC ubiquitin targeting protein.
- The study focused on late gestation lung and intestinal tissues in knockout models.
Main Results:
- Knockout of C-MYC expression in late gestation led to decreased complexity in both intestines and lungs.
- Intestinal development showed stunted villi growth, while lungs exhibited hypoplasia and disrupted alveolarization.
Conclusions:
- C-MYC is indispensable for cell expansion and complexity during late gestation lung and intestinal development.
- Transient in utero gene knockout is a valuable technique for elucidating the roles of developmentally significant genes in fetal organ development.
