Models for LRRK2-Linked Parkinsonism

Table 3

LRRK2 animal models.

Drosophila model
Transgene	Loss of TH positive neurons	Lewy body	Motor deficits	Suitability for testing disease modifying therapy	Reference
LRRK^WT,; LRRK^R1069C (R1441C); LRRK^P1, LRRK^ex1 (loss-of-function line)	ND	ND	+	ND	[53]
dLRRK(−/−), dLRRK(+/−),; dLRRK RNAi, dLRRK Tg,; R1069G(R1441G), Y1383C(Y1699C),; I1915T(I2020T)	+	ND	+	ND	[71]
dLRRKe03680, dLRRK-WT,; dLRRK- I1915T, dLRRKdf	ND	ND	+	ND	[140]
WT, G2019S, Y1699C,; G2385R	+	ND	+	+	[117]
hLRRK2(WT), hLRRK2(I1122V),; hLRRK2(Y1699C), hLRRK2(I2020T)	+	ND	+	+	[118]
WT, G2019S	+	ND	+	ND	[141]
dLRRK-WT, dLRRK-mutant(e03680)	+	ND	ND	Maybe	[142]
Caenorhabditis elegans model
LRRK2+: lrk-1(km17),; LRRK2+: lrk-1(km41),; G2019S+: lrk-1(km41); LRRK2+: lin-15(765ts); R1441C+: lin-15(765ts); G2019S+: lin-15(765ts); K1347A+: lin-15(765ts)	+	ND	+	ND	[119]
wlzIs2(WT), km4, N2(WT)	ND	ND	ND	ND	[73] (Interact with MKK6)
wlzIs1(WT), wlzIs2(WT),; wlzIs3(G2019S), wlzIs4(G2019S),; wlzIs5(R1441C), wlzIs6(KD),; wlzIs7(R1441C/KD),; wlzIs2 : wlzIs4(LRRK2/DAT::GFP)	+	ND	ND	+	[143]
LGI, lrk-1(tm1898, km41); LGII, pink-1(tm1779); LGX,; lqIs4 (ceh-10::gfp, lin-15(n765)), N2	ND	ND	ND	ND	[120] (Interact with PINK1)
N2(WT), N2(G2019S)	ND	ND	ND	+	[144]
LRK-1-K1726A(hLRRK2-I2020T); LRK-1-I1877T)(hLRRK2-I2020T)	ND	ND	ND	ND	[145] (trans-Golgi network)
Rodent model
BAC(WT)	+	−	−	ND	[27]
BAC(G2019S)	ND	ND	+	ND	[146]
LRRK2^R1441G BAC	+	−	+	Maybe	[147]
R1441C KI	ND	ND	+(AMPH-induced)	−	[148]
BAC(WT); BAC(G2019S)	+	ND	ND	Maybe	[149]
BAC(WT); BAC(G2019S)	+	ND	+	ND	[150]
WT, A53T, G2019S, KD, A53T/LRRK2WT, A53T/LRRK2G2019S, LRRK2^−/−	ND	+	ND	ND	[103]
LRRK2 null	−	ND	ND	ND	[151]
LRRK2^−/−	−	+(Kidney)	ND	ND	[122]
HSV-WTHSV-G2019SHSV-G2019S/D1994A	+	ND	ND	+	[152]
LRRK2 conditional G2019S	ND	ND	ND	Maybe	[81] (Hsp90 and LRRK2 stability)

WT: wild type; ND: not determined; GFP: Green fluorescent protein; KI, knocking in.