Skip Navigation

This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
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 ISI Web of Science
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 arrow Search for citing articles in:
ISI Web of Science (22)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Chan, E. Y. W.
Right arrow Articles by Hayden, M. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Chan, E. Y. W.
Right arrow Articles by Hayden, M. R.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Human Molecular Genetics, 2002, Vol. 11, No. 8 945-959
© 2002 Oxford University Press

Targeted disruption of Huntingtin-associated protein-1 (Hap1) results in postnatal death due to depressed feeding behavior

Edmond Y. W. Chan1,{dagger}, Jamal Nasir2,{dagger},{ddagger}, Claire-Anne Gutekunst3,{dagger}, Sarah Coleman3, Alan Maclean2, Alex Maas2, Martina Metzler1, Marina Gertsenstein4, Christopher A. Ross5, Andràs Nagy4 and Michael R. Hayden1,*

1Center for Molecular Medicine and Therapeutics, Department of Medical Genetics, Children's and Women's Hospital, University of British Columbia, Vancouver, British Columbia, Canada 2Medical Genetics Section, Molecular Medicine Centre, Western General Hospital, Edinburgh, UK 3Department of Neurology, Emory University School of Medicine, Atlanta, Georgia, USA 4Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada and 5Laboratory of Molecular Neurobiology, Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

HAP-1 is a huntingtin-associated protein that is enriched in the brain. To gain insight into the normal physiological role of HAP-1, mice were generated with homozygous disruption at the Hap1 locus. Loss of HAP-1 expression did not alter the gross brain expression levels of its interacting partners, huntingtin and p150glued. Newborn Hap1-/- animals are observed at the expected Mendelian frequency suggesting a non-essential role of HAP-1 during embryogenesis. Postnatally, Hap1-/- pups show decreased feeding behavior that ultimately leads to malnutrition, dehydration and premature death. Seventy percent of Hap1-/- pups fail to survive past the second postnatal day (P2) and 100% of Hap1-/- pups fail to survive past P9. From P2 until death, Hap1-/- pups show markedly decreased amounts of ingested milk. Hap1-/- pups that survive to P8 show signs of starvation including greatly decreased serum leptin levels, decreased brain weight and atrophy of the brain cortical mantel. HAP-1 is particularly enriched in the hypothalamus, which is well documented to regulate feeding behavior. Our results demonstrate that HAP-1 plays an essential role in regulating postnatal feeding.

* To whom correspondence should be addressed at: Center for Molecular Medicine and Therapeutics, Department of Medical Genetics, University of British Columbia Vancouver, British Columbia V5H 4H4, Canada. Tel: 604-875-3535; Fax: 604-875-3819; Email: mrh{at}cmmt.ubc.ca

{dagger} The authors wish it to be known that in their opinion, the first three authors should be regarded as joint First Authors.

{ddagger} Present Address: Section of Genetics and Informatics, University of Sheffield Medical School, Beech Hill Road, Sheffield, S10 2RX, UK


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
 J. Biol. Chem.Home page
J. Rong, S. Li, G. Sheng, M. Wu, B. Coblitz, M. Li, H. Fu, and X.-J. Li
14-3-3 Protein Interacts with Huntingtin-associated Protein 1 and Regulates Its Trafficking
J. Biol. Chem., February 16, 2007; 282(7): 4748 - 4756.
[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]

Home page
 J. Biol. Chem.Home page
J. R. McGuire, J. Rong, S.-H. Li, and X.-J. Li
Interaction of Huntingtin-associated Protein-1 with Kinesin Light Chain: IMPLICATIONS IN INTRACELLULAR TRAFFICKING IN NEURONS
J. Biol. Chem., February 10, 2006; 281(6): 3552 - 3559.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
I. Dragatsis, S. Zeitlin, and P. Dietrich
Huntingtin-associated protein 1 (Hap1) mutant mice bypassing the early postnatal lethality are neuroanatomically normal and fertile but display growth retardation
Hum. Mol. Genet., December 15, 2004; 13(24): 3115 - 3125.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
H. Li, T. Wyman, Z.-X. Yu, S.-H. Li, and X.-J. Li
Abnormal association of mutant huntingtin with synaptic vesicles inhibits glutamate release
Hum. Mol. Genet., August 15, 2003; 12(16): 2021 - 2030.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
E. Marcora, K. Gowan, and J. E. Lee
Stimulation of NeuroD activity by huntingtin and huntingtin-associated proteins HAP1 and MLK2
PNAS, August 5, 2003; 100(16): 9578 - 9583.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
S.-H. Li, Z.-X. Yu, C.-L. Li, H.-P. Nguyen, Y.-X. Zhou, C. Deng, and X.-J. Li
Lack of Huntingtin-Associated Protein-1 Causes Neuronal Death Resembling Hypothalamic Degeneration in Huntington's Disease
J. Neurosci., July 30, 2003; 23(17): 6956 - 6964.
[Abstract] [Full Text] [PDF]

Home page
 J. Histochem. Cytochem.Home page
C.-A. Gutekunst, E. R. Torre, Z. Sheng, H. Yi, S. H. Coleman, I. B. Riedel, and H. Bujo
Stigmoid Bodies Contain Type I Receptor Proteins SorLA/LR11 and Sortilin: New Perspectives on Their Function
J. Histochem. Cytochem., June 1, 2003; 51(6): 841 - 852.
[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.