Skip Navigation



Human Molecular Genetics Advance Access published online on October 20, 2004
Human Molecular Genetics, doi:10.1093/hmg/ddh328
© 2004 by Oxford University Press
This Article
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
13/24/3115    most recent
ddh328v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Dragatsis, I.
Right arrow Articles by Dietrich, P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Dragatsis, I.
Right arrow Articles by Dietrich, P.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Article

Huntingtin-associated protein 1 (Hap1) mutant mice bypassing the early postnatal lethality are neuroanatomically normal and fertile but display growth retardation

Ioannis Dragatsis Ph.D.1*, Scott Zeitlin 2, and Paula Dietrich 3

1 Department of Physiology, College of Medicine, The University of Tennessee, Health Science Center, 894 Union Avenue, rm 502, Nash BLDG, Memphis, TN 38163, USA
2 Department of Neuroscience, University of Virginia School of Medicine, Charlottesville, VA 22908, USA
3 Department of Physiology, College of Medicine, The University of Tennessee, Health Science Center, Memphis, TN 38163, USA

* To whom correspondence should be addressed.
Ioannis Dragatsis, E-mail: idragatsis{at}utmem.edu


  Abstract

Huntingtin-associated protein 1 (Hap1) is the first huntingtin interacting protein identified in a yeast two-hybrid screen. Although Hap1 expression has been demonstrated in neuronal and non-neuronal tissues, its molecular role is poorly understood. Recently, it has been shown that targeted disruption of Hap1 in mice results in early postnatal death as a result of depressed feeding behavior. Although this result clearly demonstrates an essential role of Hap1 in postnatal feeding, the mechanisms leading to this deficiency, as well as the role of Hap1 in adults, remain unclear. Here we show that Hap1 null mutants display suckling defects and die within the first days after birth due to starvation. Upon reduction of the litter size, some mutants survive into adulthood and display growth retardation with no apparent brain or behavioral abnormalities, suggesting that Hap1 function is essential only for early postnatal feeding behavior. Using a conditional gene repair strategy, we also show that the early lethality can be rescued if Hap1 expression is restored in neuronal cells before birth. Furthermore, no synergism was observed between Hap1 and huntingtin mutation in mouse development. Our results demonstrate that Hap1 has a fundamental role in regulating postnatal feeding in the first 2 weeks after birth and a non-essential role in the adult mouse.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Physiol. Rev.Home page
B. Turgeon and S. Meloche
Interpreting Neonatal Lethal Phenotypes in Mouse Mutants: Insights Into Gene Function and Human Diseases
Physiol Rev, January 1, 2009; 89(1): 1 - 26.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
J. Rong, J. R. McGuire, Z.-H. Fang, G. Sheng, J.-Y. Shin, S.-H. Li, and X.-J. Li
Regulation of intracellular trafficking of huntingtin-associated protein-1 is critical for TrkA protein levels and neurite outgrowth.
J. Neurosci., May 31, 2006; 26(22): 6019 - 6030.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.