Huntingtin Interacting Protein 1 mutations lead to abnormal hematopoiesis, spinal defects and cataracts.
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.
Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Katherine I
KI
Oravecz-Wilson
Mark J
MJ
Kiel
Lina
L
Li
Dinesh S
DS
Rao
Djenann
D
Saint-Dic
Priti D
PD
Kumar
Melissa M
MM
Provot
Kurt D
KD
Hankenson
Venkat N
VN
Reddy
Andrew P
AP
Lieberman
Sean J
SJ
Morrison
Theodora S
TS
Ross
D000818:Animals; D002386:Cataract / Q000235:genetics*; D002678:Chimera / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D018390:Gene Targeting; D006410:Hematopoiesis / Q000235:genetics* / Q000502:physiology; D006412:Hematopoietic Stem Cells; D007248:Infertility, Male / Q000209:etiology / Q000235:genetics; D008297:Male; D051379:Mice; D009154:Mutation; D017422:Sequence Analysis, DNA; D013131:Spine / Q000002:abnormalities*
D004268:DNA-Binding Proteins; C489536:Hip1 protein, mouse