An isoform of ZBP-89 predisposes the colon to colitis

Nucleic Acids Research
David J LawJ L Merchant

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-89(DeltaN)), which lacks amino terminal residues 1-127 of the full-length protein (ZBP-89(FL)). ZBP-89(DeltaN) mRNA was co-expressed with its ZBP-89(FL) cognate in gastrointestinal cell lines and tissues. Similarly, ZBP-89(DeltaN) protein was expressed. To define its function in vivo, we generated ZBP-89(DeltaN) knock-in mice by targeting exon 4 that encodes the amino terminus. Homozygous ZBP-89(DeltaN) mice, expressing only ZBP-89(DeltaN) protein, experienced growth delay, reduced viability and increased susceptibility to dextran sodium sulfate colitis. We conclude that ZBP-89(DeltaN) antagonizes ZBP-89(FL) function and that over-expression of the truncated isoform disrupts gastrointestinal homeostasis.

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Citations

Oct 5, 2006·Mammalian Genome : Official Journal of the International Mammalian Genome Society·David J LawJuanita L Merchant
Jan 25, 2011·Gut·Talin HarituniansKent D Taylor
Oct 23, 2012·American Journal of Physiology. Gastrointestinal and Liver Physiology·Bradford E BerndtJohn Y Kao
May 20, 2014·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Stefanie Hahn, Heiko Hermeking
Mar 21, 2007·Proceedings of the National Academy of Sciences of the United States of America·Michael L TressAlfonso Valencia
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Jul 3, 2007·Biochemical and Biophysical Research Communications·Meijuan ZouFan Chen
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Oct 20, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Bradford E BerndtJohn Y Kao

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Datasets Mentioned

BETA
DQ090088
DQ144540

Methods Mentioned

BETA
PCR
Transgenic

Software Mentioned

BLAST

Related Concepts

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Alternative splicing

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