Table 2. Genetic ablation of Gba2 does not correct lysosomal defects.
| Cholesterol (μmol/g ww) | Glycosphingolipids (nmol/g ww) | Activity (% wt) | ||||||
|---|---|---|---|---|---|---|---|---|
| GalCer (% wt) | GlcCer (% wt) | Cer (% wt) | GlcSph | GM3 | GM2 | β-hexo | ||
| Npc1 -/- /Gba2 -/- | 13.8 ± 0.7 | 45 ± 3** | 1096 ± 25*** | 89 ± 9 | 4.5 ± 0.5*** | 327 ± 16 | 335 ± 20* | 333 ± 13 |
| Npc1 -/- /Gba2 +/- | 14.7 ± 0.7 | 53 ± 3 | 312 ± 10* | 115 ± 7 | 2.6 ± 0.3* | 402 ± 42** | 384 ± 37** | 352 ± 18 |
| Npc1 -/- /Gba2 +/+ | 14.1 ± 0.5 | 46 ± 4** | 257 ± 22 | 102 ± 8 | 2.0 ± 0.3 | 299 ± 27 | 310 ± 23 | 364 ± 9 |
| Npc1 +/+ /Gba2 +/+ | 16.2 ± 0.4 | 100 ± 6 | 100 ± 8 | 100 ± 5 | 0.3 ± 0.0 | 3 ± 2 | 1 ± 0 | 100 ± 5 |
Levels of GalCer, GlcCer, Cer, GlcSph and gangliosides (GM3 and GM2), and activity of lysosomal enzymes β-hexosaminidase in whole brain homogenates of mice resulting from the crossing of Gba2 -/- mice with Npc1 -/- mice. Data (n = 5–6 per group) were analyzed using the Kruskal-Wallis test with post hoc Dunn’s multiple comparison test.
* P < 0.05,
** P < 0.01 and
*** P < 0.001 from Npc1 +/+/Gba2 +/+