Huntingtin Associated Protein (HAP1) knockout mice for the study of neurodegeneration in Huntington's Disease.
Mice homozygous for the Huntingtin Associated Protein (HAP1)-deficient Hap1tm1Xjl allele have neurodegeneration in areas of the hypothalamus that control feeding behavior, resulting in decreased feeding behavior, dehydration, hypoactivity, and death between two and 15 days after birth. No protein expression from the targeted gene is observed in brain tissue from homozygous mice. Hypothalamus tissue from HAP1-deficient homozygotes exhibit reduced levels of gamma-aminobutyric acid-A (GABAA; a neurotransmitter associated with feeding) and tropomyosin-related kinase A receptor tyrosine kinase (TrkA; a nerve growth factor receptor associated with neurite outgrowth). Heterozygous mice are viable and fertile with no abnormalities in HAP1 expression levels, life span, behavior, and body weight.
These huntingtin-associated protein-1 (HAP1) mutant mice may be useful in studying the hypothalamic neurodegeneration and loss of body weight in Huntington's disease (HD), neurotransmitters, microtubule-dependent transporters, intracellular trafficking, receptor tyrosine kinase and neurite function, and feeding.
Li SH et al. 2003. J Neurosci 23(17):6956-64.
Rong J et al. 2006. J Neurosci 26(22):6019-30.
Sheng G et al. Nat Med 12(5):526-33.