Analyses of substrate accumulation in <i>Gba 1</i> mutant mice.

<p>(A) The mean proportion of each GC species relative to total GC (6 GC species) in age-matched <i>Gba 1</i> mutants and WT (52 wks) visceral tissues were plotted. In the lung, GC24∶0 was significantly increased in 9V/null, whereas other species were reduced. In the liver, proportion of GC16∶0 was significantly increased in 9H/9H, but not in liver from other mutant mice. GC24∶0 had reduced proportions in 9H/9H and 9H;C* livers, whereas GC24∶1 was increased in 9V/null and 9H;C* livers compared to WT and other mutants. In the spleen, the proportion of GC20∶0 was significantly increased in 9H;C*. Reduced GC species were present in spleen of some mutant mice: GC24∶0 in 9H;C*, GC20∶0 in 9V/null, and GC24∶0 in 9V/9V. The black stars indicate that the proportion of a GC species was significantly increased and the pink stars indicate that the proportion of a GC species was reduced relative to WT. The color gradients indicate the proportion of total GC species represented by GCs with a defined FAAC. (B) The pie charts show the proportions of each GC species in 9V/null lung and WT at 52 wks. The GC24∶0 was 63% in 9V/null lung compared with 39% in WT. The proportions of the other GC species were concomitantly reduced in 9V/null lung. (C) In brain extracts, the proportion of GC18∶0 was significantly increased only in 4L;C* (black star) mice. In 9H;C* brain GC18∶0 was reduced (pink star) and long chain GC species, GC24∶0 and GC24∶1, were significantly increased (black stars). The proportion of each GC species in WT brain at 6 wks and 52 wks were included in the analyses. (D) Glusosylsphingosine concentrations in tissues from each mutant were plotted as the mean of concentration. Significant increases of glusosylsphingosine (black stars) were in 4L;C* brain and spleen, 9H;C* brain, and 9V/null lung, liver and spleen. The glucosylsphingosine levels in WT tissues at 6 wks and 52 wks were included in the analyses. The color gradient indicates glucosylsphingosine concentrations (pmol/mg tissues). The data in (A), (C) and (D) were analyzed with Tukey’s HSD test. The samples that showed significant difference from WT and other mutants (p<0.05) were marked with star (*).