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

Edmond Y W Chan, Jamal Nasir, Claire Anne Gutekunst, Sarah Coleman, Alan Maclean, Alex Maas, Martina Metzler, Marina Gertsenstein, Christopher A Ross, Andràs Nagy, Michael R. Hayden

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)945-959
Number of pages15
JournalHuman Molecular Genetics
Volume11
Issue number8
StatePublished - Apr 15 2002

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Feeding Behavior
Brain
Newborn Animals
Premature Mortality
Starvation
Leptin
Huntingtin Protein
Dehydration
Malnutrition
Hypothalamus
Atrophy
Embryonic Development
Milk
Weights and Measures
Serum

ASJC Scopus subject areas

  • Genetics

Cite this

Chan, E. Y. W., Nasir, J., Gutekunst, C. A., Coleman, S., Maclean, A., Maas, A., ... Hayden, M. R. (2002). Targeted disruption of Huntingtin-associated protein-1 (Hap1) results in postnatal death due to depressed feeding behavior. Human Molecular Genetics, 11(8), 945-959.

Targeted disruption of Huntingtin-associated protein-1 (Hap1) results in postnatal death due to depressed feeding behavior. / Chan, Edmond Y W; Nasir, Jamal; Gutekunst, Claire Anne; Coleman, Sarah; Maclean, Alan; Maas, Alex; Metzler, Martina; Gertsenstein, Marina; Ross, Christopher A; Nagy, Andràs; Hayden, Michael R.

In: Human Molecular Genetics, Vol. 11, No. 8, 15.04.2002, p. 945-959.

Research output: Contribution to journalArticle

Chan, EYW, Nasir, J, Gutekunst, CA, Coleman, S, Maclean, A, Maas, A, Metzler, M, Gertsenstein, M, Ross, CA, Nagy, A & Hayden, MR 2002, 'Targeted disruption of Huntingtin-associated protein-1 (Hap1) results in postnatal death due to depressed feeding behavior', Human Molecular Genetics, vol. 11, no. 8, pp. 945-959.
Chan EYW, Nasir J, Gutekunst CA, Coleman S, Maclean A, Maas A et al. Targeted disruption of Huntingtin-associated protein-1 (Hap1) results in postnatal death due to depressed feeding behavior. Human Molecular Genetics. 2002 Apr 15;11(8):945-959.
Chan, Edmond Y W ; Nasir, Jamal ; Gutekunst, Claire Anne ; Coleman, Sarah ; Maclean, Alan ; Maas, Alex ; Metzler, Martina ; Gertsenstein, Marina ; Ross, Christopher A ; Nagy, Andràs ; Hayden, Michael R. / Targeted disruption of Huntingtin-associated protein-1 (Hap1) results in postnatal death due to depressed feeding behavior. In: Human Molecular Genetics. 2002 ; Vol. 11, No. 8. pp. 945-959.
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