An isoform of ZBP-89 predisposes the colon to colitis

Author： Law David J. Labut Edwin M. Adams Rachael D. Merchant Juanita L.

ISSN： 1362-4962

Source： Nucleic Acids Research, Vol.34, Iss.5, 2006-01, pp. : 1342-1350

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