, 2007, Björkqvist et al., 2008, Ginés et al., 2006, Jenkins et al., 2005, Kuhn et al., 2007, Luthi-Carter et al., 2002, Menalled et al., 2000, Southwell et al., 2009, Strand et al., 2007, Walker et al., 2008 and Woodman et al., 2007). In this review we have focused on specific pathological aspects of HD

to compare and contrast models. HD in patients is characterized by motor, cognitive, and behavioral symptoms, and assays testing these broad categories are used to measure progression of pathology in HD mice. Motor phenotypes have been tested in a number of HD model mice, including limb clasping upon tail Histone Methyltransferase inhibitor suspension, basal activity level, gait abnormalities, balance beam traversing time, swimming speed, suspended horizontal beam turning, and latency to remain on a fixed-speed or accelerating rotarod. The rotarod, in particular, has proven to be a robust quantitative measurement of balance and coordination deficits for which nearly every HD model mouse has demonstrated a www.selleckchem.com/products/OSI-906.html deficiency. N-terminal transgenic mice consistently display an early onset of severe motor symptoms. R6/2 mice swim poorly by 5 weeks of age and show beam-walking and rotarod

deficiencies by 6 weeks, both of which progressively worsen with age (Carter et al., 1999). R6/1 mice experience clear rotarod deficiency at 18 weeks (Hodges et al., 2008) with an earlier (13 week) onset of failure to turn around on a suspended horizontal rod (van Dellen et al., 2000), Terminal deoxynucleotidyl transferase and N171-82Q mice display a subtle but progressive rotarod phenotype at 3 months (Schilling et al., 1999). Full-length transgenic models display delayed motor symptoms compared to N-terminal transgenics; YAC72 mice do not display a significant rotarod phenotype until 16 months (Seo et al., 2008), while YAC128 mice decline starting at 6–7 months (Slow et al., 2003 and Van

Raamsdonk et al., 2005c). BACHD transgenics do show a significant reduction in rotarod latency as early as 4 weeks of age, but they do not precipitously decline in performance until 28 weeks; this is in contrast to R6/2 rotarod performance, which rapidly declines once a difference is measured (Menalled et al., 2009). Knockin mice do not always display the characteristic motor phenotype seen in transgenic models, despite some strains carrying as many CAG repeats as R6/2 mice (∼150) and having twice the gene dose as most transgenic strains (behavioral experiments carried out in knockin mice typically use homozygotes). This could reflect differences in chromosomal context, transgene expression, the chimeric nature of knockin Htt inserts, or strain background. HdhQ140 rotarod latency appears at 4 months at 30 rpm on a fixed-speed rotarod ( Hickey et al., 2008), but another group reported no accelerating rotarod phenotype through 6 months ( Dorner et al.