Basic—Alimentary TractCdx2 Levels Modulate Intestinal Epithelium Maturity and Paneth Cell Development
Section snippets
Generation of Villin-Cdx2 Transgenic Mice
Mouse Cdx2 complementary DNA (cDNA) with an N-terminal FLAG-tag19 was subcloned into a pCMV-Tag3c (Stratagene, La Jolla, CA) plasmid. The 12.4-kb mouse Villin promoter was then subcloned before the cDNA to generate the final Villin-(FLAG)-Cdx2 construct. The Villin-Cdx2 DNA was linearized and injected into the male pronuclei of fertilized eggs and implanted into pseudopregnant females by the Transgenic and Chimeric Mouse Core Facility at the University of Pennsylvania. Founder animals were
Development of Transgenic Mouse Lines Overexpressing Cdx2 in the Mouse Intestine
Transgenic mice were generated using the 12.4-kb mouse villin regulatory sequences (kindly provided by Dr. Deborah Gumucio, University of Michigan) to drive expression of a mouse Cdx2 complementary DNA with an N-terminal FLAG tag that differentiates transgenic from endogenous Cdx2 (Figure 1A).22 Four distinct founders expressing the transgene were obtained from 2 injections. All 4 lines expressed the transgene messenger RNA (mRNA) as detected by PCR, and levels of total intestinal Cdx2 protein
Discussion
It has been established that the homeodomain transcription factor Cdx2 plays a critical role in regulating intestinal epithelial differentiation and function.12 Our transgenic mice unexpectedly display a complex phenotype, suggesting Cdx2 plays important roles in other intestinal cell processes.
Acknowledgments
We thank William Hockheimer and Abena Kwaa for their technical support.
At the time of the study, Rong-Jun Guo and Shinsuke Funakoshi were at the Division of Gastroenterology, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
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Conflicts of interest The authors disclose no conflicts.
Funding This work was supported by National Institute of Diabetes and Digestive and Kidney Diseases grants DK068366 and DK085551 (JL), an National Cancer Institute Program Project P01 CA098101, and Core Facilities of the Center for Molecular Studies in Digestive and Liver Disease at the University of Pennsylvania (P30-DK50306).