Transient in utero knockout (TIUKO) of C-MYC affects late lung and intestinal development in the mouse.
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.
Cohen
J Craig
JC
Department of Medicine, LSU School of Medicine, 533 Bolivar St, New Orleans, USA. ccohen@lsuhsc.edu
Scott
Donald K
DK
Miller
James
J
Zhang
Jianxuan
J
Zhou
Pengbo
P
Larson
Janet E
JE
D000256:Adenoviridae / Q000235:genetics; D000257:Adenoviridae Infections / Q000235:genetics; D000818:Animals; D002460:Cell Line; D016373:DNA, Antisense / Q000235:genetics; D004279:DNA, Viral / Q000235:genetics; D005314:Embryonic and Fetal Development / Q000235:genetics; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D018014:Gene Transfer Techniques; D016259:Genes, myc / Q000502:physiology; D007422:Intestines / Q000196:embryology* / Q000502:physiology / Q000821:virology; D008168:Lung / Q000196:embryology* / Q000502:physiology / Q000821:virology; D051379:Mice; D018345:Mice, Knockout; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000502:physiology; D025801:Ubiquitin
D016373:DNA, Antisense; D004279:DNA, Viral; D016271:Proto-Oncogene Proteins c-myc; D025801:Ubiquitin