The apparent increase in the sensitivity of http://www.selleckchem.com/products/dorsomorphin-2hcl.html the detection of age-dependent onset of memory impairment using tone fear conditioning makes this test an attractive potential diagnostic tool during evaluation of the efficacy of potential therapeutics on memory function in the CRND8 mouse model. Materials and methods Mice The transgenic CRND8 mice over-express mutant forms of human APP genes (Swedish; KM670/671NL + Indiana; V717F) [26,38] implicated in AD [39,40]. This model shows rapid onset of extra-cellular A?? deposits at 2.5 to 3 months of age, with coinciding impairment in spatial reference memory . Dense-core A?? plaques and neuritic pathology appear at five months .
Three cohorts of transgenic (Tg) CRND8 and non-transgenic (nTg) littermates (hybrid genetic background, C57BL/6//C3H) at ages three (N = 27, 13/14 Tg/nTg), six (N = 28, 11/17 Tg/nTg), and 12 (N = 24, 11/13 Tg/nTg) months were used. The physical condition and sensorimotor propensities of the CRND8 mice did not differ from their control nTg littermates within the studied age range as evaluated in the SHIRPA (SmithKline Beecham Pharmaceuticals; Harwell, MRC Mouse Genome Centre and Mammalian Genetics Unit; Imperial College School of Medicine at St Mary’s; Royal London Hospital, St Bartholomew’s and the Royal London School of Medicine; Phenotype Assessment) phenotyping screen (data not shown). The cohorts within each genotype were female biased (median for males = 3.5, for females = 9). The mice were genotyped at weaning by analysis of tail DNA with a human APP hybridization probe, as described previously .
They were housed in same-sex groups of two to four under standard laboratory conditions (12:12 hours light/dark cycle, lights on at 0600 hours) with a room temperature of 21??C, and water and food available ad libitum. All tests were performed AV-951 during the light phase between 09:00 and 14:00 hours. All procedures were approved by the Institutional Animal Care and Use Committee of Mayo Clinic Jacksonville Pazopanib and are in accordance with Association for Assessment and Accreditation of Laboratory Animal Care International (AAALAC) and the National Institutes of Health Guide for the Care and Use of Laboratory Animals guidelines. Primary neurological and sensorimotor examination The SHIRPA protocol [41,42] involves a series of tests assessing the physical condition of the mice. The following phenotypes are measured: (1) body position in a cage, respiration, tremor, transfer arousal, palpebral closure, piloerection, (2) reflexes – touch escape, pinna reflex, trunk curl, limb grasping, visual placing, negative geotaxis and righting reflex, and (3) grip strength. The screen takes altogether about five to seven minutes per mouse.