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 language | English |
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Pages (from-to) | 945-959 |
Number of pages | 15 |
Journal | Human Molecular Genetics |
Volume | 11 |
Issue number | 8 |
DOIs | |
Publication status | Published - 15 Apr 2002 |
Keywords
- animal nutritional physiological phenomena
- animals
- animals, suckling
- body constitution
- eating
- homozygote
- hypothalamus
- leptin
- mice
- microtubule-associated proteins
- mutagenesis, site-directed
- nerve tissue proteins
- neurons
- nuclear proteins
- starvation