@article{3744f276455443c8ba90dae00954ed57,
title = "An isoform of ZBP-89 predisposes the colon to colitis",
abstract = "Alternative splicing enables expression of functionally diverse protein isoforms. The structural and functional complexity of zinc-finger transcription factor ZBP-89 suggests that it may be among the class of alternatively spliced genes. We identified a human ZBP-89 splice isoform (ZBP-89δN), which lacks amino terminal residues 1-127 of the full-length protein (ZBP-89 FL). ZBP-89δN mRNA was co-expressed with its ZBP-89 FL cognate in gastrointestinal cell lines and tissues. Similarly, ZBP-89δN protein was expressed. To define its function in vivo, we generated ZBP-89δN knock-in mice by targeting exon 4 that encodes the amino terminus. Homozygous ZBP-89δN mice, expressing only ZBP-89δN protein, experienced growth delay, reduced viability and increased susceptibility to dextran sodium sulfate colitis. We conclude that ZBP-89δN antagonizes ZBP-89 FL function and that over-expression of the truncated isoform disrupts gastrointestinal homeostasis.",
author = "Law, {David J.} and Labut, {Edwin M.} and Adams, {Rachael D.} and Merchant, {Juanita L.}",
note = "Funding Information: The authors gratefully acknowledge the expertise of the University of Michigan Transgenic Animal Model Core, especially Thom Saunders, Linda Samuelson and Elizabeth Hughes. The authors also thank members of the DNA Sequencing Core and the Unit for Laboratory Animal Medicine at the University of Michigan, and Kathy McClinchey for assistance with histology. Proteomics data were provided by the Michigan Proteome Consortium (www.proteomeconsortium.org) which is supported in part by funds from the Michigan Life Sciences Corridor. Specifically, valuable assistance with 2D gel electrophoresis was provided by Jennifer Callahan. This research is supported in part by the National Institutes of Health through the University of Michigan{\textquoteright}s Cancer Center Support Grant (5 P30 CA46592) and the University of Michigan Gastrointestinal Peptide Research Center (DK-34533). Art Tessier and Gail Kelsey provided administrative support. Stacey Ehrenberg provided technical assistance. This work was supported by grants from the National Institutes of Health to D.J.L. (R21 DK65004-01) and J.L.M. (RO1-DK55732). Funding to pay the Open Access publication charges for this article was provided by NIH grant RO1-DK55732 (J.L.M.).",
year = "2006",
doi = "10.1093/nar/gkl022",
language = "English (US)",
volume = "34",
pages = "1342--1350",
journal = "Nucleic acids research",
issn = "0305-1048",
publisher = "Oxford University Press",
number = "5",
}