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The itchy locus encodes a novel ubiquitin protein ligase that is disrupted in a18H mice

Nature Genetics volume 18, pages 143–146 (1998)Cite this article

Abstract

Non-agouti-lethal 18H (a18H) mice are dark agouti with black pinna hairs. What makes these mice unique is that they develop a spectrum of immunological diseases not seen in other agouti mutant mice1. On the JU/Ct background, a18H mice develop an inflammatory disease of the large intestine. On the C57BL/6J background, they develop a fatal disease characterized by pulmonary chronic interstitial inflammation and alveolar proteinosis, inflammation of the glandular stomach and skin resulting in scarring due to constant itching, and hyperpla-sia of lymphoid cells, haematopoietic cells and the forestomach epithelium. Previous studies suggested that the a18H mutation results from a paracentric inversion that affects two loci: agouti and another, as yet unidentified locus designated itchy (the provisional gene symbol is Itch), that is responsible for the immunological phenotype of a18H mice1. Here we confirm that a18H results from an inversion and show that Itch encodes a novel E3 ubiquitin protein ligase, a protein involved in ubiqui-tin-mediated protein degradation. Our results indicate that ubiquitin-dependent proteolysis is an important mediator of the immune response in vivo and provide evidence for Itch's role in inflammation and the regulation of epithelial and haematopoietic cell growth.

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Author notes

  1. William L. Perry

    Present address: Myriad Genetics, Inc., 390 Wakara Way, Salt Lake City, Utah, 84108, USA

Authors and Affiliations

  1. Mammalian Genetics Laboratory, ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, Frederick, Maryland, 21702-1201, USA

    William L. Perry, Carolyn M. Hustad, Debra A. Swing, T. Norene O'Sullivan, Nancy A. Jenkins & Neal G. Copeland

Authors
  1. William L. Perry
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  2. Carolyn M. Hustad
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  3. Debra A. Swing
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  4. T. Norene O'Sullivan
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  5. Nancy A. Jenkins
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  6. Neal G. Copeland
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Corresponding author

Correspondence to Neal G. Copeland.

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Perry, W., Hustad, C., Swing, D. et al. The itchy locus encodes a novel ubiquitin protein ligase that is disrupted in a18H mice. Nat Genet 18, 143–146 (1998). https://doi.org/10.1038/ng0298-143

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