Article Figures & Data
Figures
- Figure 1.
Genetic modulation of mouse Fyn alters the extent of hAPPFAD/Aβ-induced reductions in SIPT and premature mortality. FYN refers to the Fyn transgene, and fyn refers to the endogenous gene. n.s., Not significant. *p = 0.001; **p < 0.0005 versus NTG wild-type littermate controls. A, Overexpressing Fyn exacerbated SIPT reductions in hAPPlow mice (n = 5-9 mice/genotype; age, 6-8 months). B, Confocal microscopic images illustrating SIPT in the OML of an NTG mouse (top) and an hAPPlow/FYN doubly TG mouse (bottom). C, Ablating Fyn reduced SIPT levels but also prevented additional SIPT reductions in hAPPhigh mice (n = 5-8 mice/genotype; age, 4-5 months). D, Overexpressing Fyn did not alter Aβ levels in hAPPlow mice (n = 5-9 mice/genotype; age, 6-8 months). E, Ablating Fyn did not alter Aβ levels in hAPPhigh mice (n = 5-8 mice/genotype; age, 4-5 months). F, SIPT levels correlated inversely with Aβ1-42 levels and Aβ1-42/Aβ1-x ratios in hAPPhigh mice on the fyn+/+, but not fyn-/-, background (age, 4-5 months). G, Comparable plaque load in hAPPhigh mice on fyn+/+ and fyn-/- backgrounds (n = 7-8 mice/genotype; age, 8-10 months). H, I, Proportion of mice that died prematurely in each of the groups indicated during the first 6 months postnatally (percentage of 38-64 mice/genotype). Husbandry conditions were similar for all groups.
- Figure 2.
Aberrant axonal sprouting in hAPPFAD mice depends on age and hAPPFAD expression levels. A, Photomicrographs of GAP-43-IR in the hippocampus of a 6-month-old NTG mouse and an hAPPhigh TG littermate. Prominent aberrant sprouting is evident in the molecular layer of the hAPPhigh mouse (arrow). B, In hAPPhigh mice, GAP-43-IR in this layer further increased with age. C, Photomicrographs showing normal GAP-43-IR in the hippocampus of a 6-month-old NTG mouse and an hAPPlow TG littermate. D, Quantitation of GAP-43-IR in 6-month-old hAPPhigh mice revealed a 60% increase in the OML and a 13% increase in the MML (n = 10-13 mice/genotype). *p < 0.05; **p < 0.0001 versus NTG wild-type littermates. E, Quantitation of GAP-43-IR in the OML and MML revealed no aberrant sprouting in hAPPlow mice (n = 11-13 mice/genotype). mo, Months; IML, inner molecular layer.
- Figure 3.
Genetic modulation of Fyn does not affect hAPP/Aβ-induced aberrant sprouting. A, Comparable increases in GAP-43-IR in the OML of hAPPhigh mice on the fyn+/+ and fyn-/- background (n = 5-8 mice/genotype; age, 4-5 months). *p < 0.005. B, GAP-43-IR did not correlate with hippocampal Aβ1-42 levels or Aβ1-42/Aβ1-x ratios in hAPPhigh mice on the fyn+/+ and fyn-/- backgrounds. C, Overexpressing Fyn did not increase GAP-43-IR levels in hAPPlow mice (n = 5-9 mice/genotype; age, 6-8 months).
