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

Authors: Chan, EY  Nasir, J  Gutekunst, CA  Coleman, S  Maclean, A  Maas, A  Metzler, M  Gertsenstein, M  Ross, CA  Nagy, A  Hayden, MR 
Citation: Chan EY, etal., Hum Mol Genet 2002 Apr 15;11(8):945-59.
Pubmed: (View Article at PubMed) PMID:11971876

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.

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CRRD Object Information
CRRD ID: 1302538
Created: 2004-10-13
Species: All species
Last Modified: 2004-10-13
Status: ACTIVE



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