Mice defective in interferon signaling help distinguish between primary and secondary pathological pathways in a mouse model of neuronal forms of Gaucher disease

Table 3 Genes associated with primary neuropathological pathways

Gene	WT + CBE versus WT + PBS	WT + CBE versus MyTrMaSt + PBS	CBE + SRT
	Fold-change	Fold-change
SL metabolism
Ugt8a	− 3.46	− 3.97	++
Fa2h	− 2.00	− 2.00	++
Gal3st1	− 2.42	− 1.33	n.s.
Cholesterol metabolism
Msmo1	− 2.28	− 2.27	++
Ch25h	20.3	12.8	+
Dhcr7	− 2.78	− 1.62	n.s.
Tm7sf2	− 2.05	− 1.44	n.s.
Hmgcs1	− 2.63	− 2.07	n.s.
Fdps	− 2.90	− 2.10	n.s.
Lipoprotein metabolism and lipid droplets
Apoc1	2.76	2.42	++
Plin2¹	5.57	2.90	++
Plin4	9.97	41.3	++
Apoe	1.85	1.56	+
Metalloproteinases
Adam8	6.20	5.20	+
Mt1¹	3.80	3.40	++
Mt2	6.30	4.80	++
Lysosome
Gusb¹	6.08	5.88	n.s.
Hexb	3.43	3.17	+
Naglu	2.60	2.27	+
CtsD¹	4.48	4.68	+
Ctsz	6.62	5.30	+
Galns	2.88	2.39	n.s.
Neuronal genes
Ccdc160	− 2.33	− 2.11	n.s.
Glra1	− 2.04	− 2.63	n.s.
Srpk1	− 2.45	− 2.05	n.s.
Inflammation (chemokines)
Ccl3	39.7	55.5	+
Ccl4	49.2	32.7	+
Cx3cr1¹	3.70	2.10	n.s.
Inflammation (TNF)
Tnfrsf1a	3.02	4.68	+
Tnfaip8l2	4.08	4.02	+
Slamf9	16.1	15.0	+
Ltbr	2.33	3.08	n.s.
Litaf	3.32	2.32	n.s.
Inflammation (TGF)
Tgfbr2	2.02	2.81	n.s.
Cd109	8.53	10.4	++
Inflammation (IL6)
Il6ra	5.03	3.08	n.s.
Osmr	4.73	9.70	+
Inflammation (Microglia)
Lyz2	13.2	7.80	+
Mpeg1	9.07	11.5	+
Cd68	8.08	13.9	+
Inflammation (Astrocytes)
Agt	2.10	2.80	n.s.
Gfap	9.86	9.69	+
Complement
C1qa	4.16	4.61	+
C1qb	5.55	5.11	+
C1qc	7.53	5.17	+
C4b	7.35	7.08	+
C5ar1¹	27. 7	14.8	+
DAMs
Trem2	6.12	8.88	+
Tyrobp¹	6.65	6.55	+
Cd63	3.70	3.20	+
Clec7a	43.9	31.3	+
Csf1	3.14	2.20	-
Itgax	61.1	39.6	-
Others
St14	3.28	4.85	-
Mrpl35	− 2.33	− 2.03	n.s.

Genes whose levels were changed < 2-fold in MyTrMaSt mice compared with WT mice. Fold-changes were all statistically significant (p < 0.01). The right-hand column indicates genes that reverted to control levels upon SRT (from Blumenreich et al., submitted for publication; see Discussion).
n.s. not significant
¹ Validated by PCR: WT + CBE versus WT + PBS, fold-change 7.9 ± 3.1 (Plin2), 1.8 ± 0.2 (Mt1), 5.9 ± 1.4 (Gusb), 5.9 ± 1.4 (CtsD), 3.1 ± 0.6 (Cx3cr1), 31.4 ± 3.8 (C5ar1), 11.4 ± 3.0 (Tyrobp). MyTrMaSt + CBE versus MyTrMaSt + PBS, fold-change 4.1 ± 1.3 (Plin2), 1.9 ± 0.2 (Mt1), 6.7 ± 0.5 (Gusb), 5.2 ± 0.5 (CtsD), 3.2 ± 0.4 (Cx3cr1), 15.9 ± 1.2 (C5ar1), 9.1 ± 0.5 (Tyrobp)
+ Genes whose expression were reduced upon SRT, yet remained upregulated
++ Genes that reverted to control levels upon SRT
- Genes whose expression was not affected upon SRT

ISSN: 1742-2094