PMC:1283364 / 33651-35386
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{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/1283364","sourcedb":"PMC","sourceid":"1283364","source_url":"http://www.ncbi.nlm.nih.gov/pmc/1283364","text":"Robust Transgene Suppression in Older Mice with Preexisting Amyloid Pathology\n(A) Cortical homogenates from 6- to 12-mo-old animals used for pathology studies described below (line 107) were immunoblotted with human-specific antibody 6E10 to examine transgene suppression following 3 or 6 mo of dox treatment. The blot was co-immunostained for endogenous superoxide dismutase 1 (SOD1) as a control for loading.\n(B) Quantitation of signal intensity from the Western blot shown in (A). Transgenic APP levels are significantly suppressed following 3 or 6 mo of dox treatment (96.9% and 97.6%, respectively). *, p \u003c 0.001 compared to 6-mo-old untreated animals, Tukey post-hoc test applied to significant effect of group ANOVA F 3,12 = 107.22, p \u003c 0.001. These data demonstrate that strong transgene suppression is attained both before and after the onset of amyloid pathology (see Figure 1 for predeposit experiments).\n(C) Experimental design. To examine the effects of chronic Aβ suppression on amyloid pathology after the onset of deposition, we compared untreated controls harvested at 6 and 9 mo of age to animals placed on dox at 6 mo of age and harvested after 3 or 6 mo of treatment.\n(D) Dox treatment leads to rapid transgene suppression even in 6-mo-old tTA/APP mice. Immunostaining with 6E10 shows APPswe/ind levels are dramatically reduced in 6-mo-old mice treated for 1 wk with dox (upper panel). A separate blot was immunostained for APP C-terminal fragments with CT15 antibody to show that the precursors to Aβ cleavage are decreased in parallel with the full-length protein (middle panel). Costaining for superoxide dismutase 1 was used as an internal control for loading (lower panel, taken from bottom half of 6E10 blot).","divisions":[{"label":"title","span":{"begin":0,"end":77}},{"label":"p","span":{"begin":78,"end":410}},{"label":"p","span":{"begin":411,"end":915}},{"label":"p","span":{"begin":916,"end":1187}}],"tracks":[]}