Exploratory activity and fear conditioning abnormalities develop early in R6/2 Huntington's disease transgenic mice.
The Huntington's disease R6/2 transgenic mouse model, containing exon 1 of the human huntingtin gene with a greatly increased CAG repeat length, shows multiple effects of the altered polyglutamine in the resultant protein. The authors report that exploratory and fear conditioning behavioral changes appear well before the onset of obvious pathology. The first differences in exploratory and fear conditioning behavior emerge by 4 and 5 weeks of age, respectively. These behaviors correlate with the earliest neurochemical and molecular changes previously reported and provide insight into functional mechanisms by which cellular and subcellular disease changes may mediate neurological symptoms. These studies provide behavioral protocols suitable for high-throughput screening of therapeutic agents.
Bolivar
Valerie J
VJ
Wadsworth Center, David Axelrod Institute, New York State Department of Health, Albany, New York 12201-2002, USA. bolivar@wadsworth.org
Manley
Kevin
K
Messer
Anne
A
D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D003214:Conditioning, Classical / Q000502:physiology*; D003430:Cross-Sectional Studies; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000502:physiology*; D005239:Fear / Q000502:physiology*; D005260:Female; D006816:Huntington Disease / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D009043:Motor Activity / Q000502:physiology