Journal Article

Huntingtin Interacting Protein 1 mutations lead to abnormal hematopoiesis, spinal defects and cataracts

Katherine I. Oravecz-Wilson, Mark J. Kiel, Lina Li, Dinesh S. Rao, Djenann Saint-Dic, Priti D. Kumar, Melissa M. Provot, Kurt D. Hankenson, Venkat N. Reddy, Andrew P. Lieberman, Sean J. Morrison and Theodora S. Ross

in Human Molecular Genetics

Volume 13, issue 8, pages 851-867
Published in print April 2004 | ISSN: 0964-6906
Published online March 2004 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/ddh102
Huntingtin Interacting Protein 1 mutations lead to abnormal hematopoiesis, spinal defects and cataracts

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Huntingtin Interacting Protein 1 (HIP1) binds clathrin and AP2, is overexpressed in multiple human tumors, and transforms fibroblasts. The function of HIP1 is unknown although it is thought to play a fundamental role in clathrin trafficking. Gene-targeted Hip1−/− mice develop premature testicular degeneration and severe spinal deformities. Yet, although HIP1 is expressed in many tissues including the spleen and bone marrow and was part of a leukemogenic translocation, its role in hematopoiesis has not been examined. In this study we report that three different mutations of murine Hip1 lead to hematopoietic abnormalities reflected by diminished early progenitor frequencies and resistance to 5-FU-induced bone marrow toxicity. Two of the Hip1 mutant lines also display the previously described spinal defects. These observations indicate that, in addition to being required for the survival/proliferation of cancer cells and germline progenitors, HIP1 is also required for the survival/proliferation of diverse types of somatic cells, including hematopoietic progenitors.

Journal Article.  10818 words.  Illustrated.

Subjects: Genetics and Genomics

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