This Article Full Text Full Text (PDF) Supplemental material Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hyun, T. S. Articles by Ross, T. S. Search for Related Content PubMed PubMed Citation Articles by Hyun, T. S. Articles by Ross, T. S.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, May 2004, p. 4329-4340, Vol. 24, No. 10
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.10.4329-4340.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Hip1-related Mutant Mice Grow and Develop Normally but Have Accelerated Spinal Abnormalities and Dwarfism in the Absence of HIP1

Department of Internal Medicine,¹ Graduate Program in Cellular and Molecular Biology, University of Michigan Medical School, Ann Arbor, Michigan 48109²

Received 25 November 2003/ Returned for modification 24 January 2004/ Accepted 11 February 2004

In mice and humans, there are two known members of the Huntingtin interacting protein 1 (HIP1) family, HIP1 and HIP1-related (HIP1r). Based on structural and functional data, these proteins participate in the clathrin trafficking network. The inactivation of Hip1 in mice leads to spinal, hematopoietic, and testicular defects. To investigate the biological function of HIP1r, we generated a Hip1r mutant allele in mice. Hip1r homozygous mutant mice are viable and fertile without obvious morphological abnormalities. In addition, embryonic fibroblasts derived from these mice do not have gross abnormalities in survival, proliferation, or clathrin trafficking pathways. Altogether, this demonstrates that HIP1r is not necessary for normal development of the embryo or for normal adulthood and suggests that HIP1 or other functionally related members of the clathrin trafficking network can compensate for HIP1r absence. To test the latter, we generated mice deficient in both HIP1 and HIP1r. These mice have accelerated development of abnormalities seen in Hip1 -deficient mice, including kypholordosis and growth defects. The severity of the Hip1r/Hip1 double-knockout phenotype compared to the Hip1 knockout indicates that HIP1r partially compensates for HIP1 function in the absence of HIP1 expression, providing strong evidence that HIP1 and HIP1r have overlapping roles in vivo.

Supplemented material for this article may be found at http://mcb.asm.org

This article has been cited by other articles:

• Graves, C. W., Philips, S. T., Bradley, S. V., Oravecz-Wilson, K. I., Li, L., Gauvin, A., Ross, T. S. (2008). Use of a Cryptic Splice Site for the Expression of Huntingtin Interacting Protein 1 in Select Normal and Neoplastic Tissues. Cancer Res. 68: 1064-1073 [Abstract] [Full Text]  
• Bradley, S. V., Hyun, T. S., Oravecz-Wilson, K. I., Li, L., Waldorff, E. I., Ermilov, A. N., Goldstein, S. A., Zhang, C. X., Drubin, D. G., Varela, K., Parlow, A., Dlugosz, A. A., Ross, T. S. (2007). Degenerative phenotypes caused by the combined deficiency of murine HIP1 and HIP1r are rescued by human HIP1. Hum Mol Genet 16: 1279-1292 [Abstract] [Full Text]