Transient in utero knockout (TIUKO) of C-MYC affects late lung and intestinal development in the mouse

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 epit...

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Bibliographic Details
Published in:BMC developmental biology 2004-04, Vol.4 (1), p.4-4
Main Authors: Cohen, J Craig, Scott, Donald K, Miller, James, Zhang, Jianxuan, Zhou, Pengbo, Larson, Janet E
Format: Article
Language:English
Subjects:
Adenoviridae - genetics
Adenoviridae Infections - genetics
Adenovirus
Animals
Cell Line
DNA, Antisense - genetics
DNA, Viral - genetics
Embryonic and Fetal Development - genetics
Female
Gene Expression Regulation, Developmental - genetics
Gene Transfer Techniques
Genes, myc - physiology
Intestines - embryology
Intestines - physiology
Intestines - virology
Lung - embryology
Lung - physiology
Lung - virology
Mice
Mice, Knockout
Proto-Oncogene Proteins c-myc - genetics
Proto-Oncogene Proteins c-myc - physiology
Ubiquitin
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Summary: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. 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. 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.
ISSN:1471-213X
1471-213X
DOI:10.1186/1471-213X-4-4