TABLE 6.

Mouse LRRK2 KI models.

Mouse LRRK2 KI models	Author(s), year(s)	Model (species, gene, mutation, tag)	Background (strain)	DA neuronal loss	Locomotor/behavioral changes	Other notes
1	Giesert et al., 2017	Mouse LRRK2 R1441C KI.	C57BL/6J (backcrossed).	No loss in SN up to 28 months.	Increased time on pole test, increased total slips (beam test), and increased time on ladder test at >24 months. Gait analysis shows decreased front paw angle on CatWalk at 26 months. Reduction in odor sensitivity and discrimination at 24–26 months. Decrease in time spent swimming on forced swim test at 8–15 months. Tail suspension test altered at 8 months in females (See Giesert for important negative data).	No synuclein or tau pathology. R1441C KI line has locomotor or behavioral symptoms that may indicate prodromal/early phase of PD in humans.
2	(Steger et al., 2016) (Eli Lilly)	Mouse LRRK2 G2019S KI.	C57BL/6J.	Not assessed.	Not assessed.
3	(Steger et al., 2016) (Michael J. Fox Foundation)	Mouse LRRK2 A2016T KI (kinase inhibitor resistant).	C57BL/6NJ.	Not assessed.	Not assessed.
4	Ito et al., 2016	Mouse LRRK2 Kinase Dead (D2017A) KI.	C57BL/6J (backcrossed).	Not assessed.	Not assessed.
5	Ito et al., 2016; Zhou et al., 2018	Mouse LRRK2 [S910A + S935A] KI.	C57BL/6 (backcrossed).	Not assessed.	Increased latency to fall at 40 rpm but not 50 rpm on rotarod (Zhou).	Reduced astrocytes in dorsolateral striatum at 18 months. Increased α-synuclein in dorsolateral striatum at 3 months.
6	(Matikainen-Ankney et al., 2016, 2018) (Eli Lilly)	Mouse LRRK2 G2019S KI.	C57BL/6NTac.	Not assessed.	More resistant to chronic social defeat stress (CSDS). Altered self-care based on grooming time. No difference on rotarod or elevated plus maze test (2018).	Increased sEPSC frequency in dorsal striatal SPNs at P21 (restored with kinase inhibition). SPNs at P21 had greater spine head width (2016). Decreased sEPSC amplitude in NAc SPNs. Mice lack CP-AMPAR at baseline and post-CSDS. Unable to form LTP in dorsal striatal SPNs (2018).
7	(Matikainen-Ankney et al., 2016) (Eli Lilly)	Mouse LRRK2 Kinase Dead (D2017A) KI.	C57BL/6NTac.	Not assessed.	Not assessed.
8	Liu et al., 2014	Mouse LRRK2 R1441G KI.	C57BL6/N (backcrossed).	No loss in SNpc up to 18–22 months. No TH cell loss in striatum at 18–22 months.	No changes at 3 and 12 months in open field.	No synuclein, tau or ubiquitin pathology. Alterations in open field and DA uptake in response to reserpine (depletes DA in striatum).
9	Dächsel et al., 2010; Beccano-Kelly et al., 2014; Yue et al., 2015; Volta et al., 2017	Mouse LRRK2 G2019S KI.	C57BL/6.	No loss in SN up to 18–20 months (Yue).	Increased distance traveled and latency to fall at 6 months (not seen at 12 months) (Yue). Increased rearing at 6 months (not seen at 12 months) (Volta).	Increased phospho-tau in corpus callosum and midbrain at 18 months. Decrease in extracellular DA at 12 months. Dose dependent increase in kinase activity. Decrease fission/fusion of mitochondria at 15 months (Yue). Increased sEPSC frequency in DIV21 cortical cultures. Reduced synapsin 1 phosphorylatio in DIV21 cortical cultures (Beccano-Kelly). Increased sEPSC frequency in striatal SPNs at 1–3 months and increased dopamine transmission (Volta).
10	Herzig et al., 2011; Longo et al., 2014	Mouse LRRK2 G2019S KI.	C57BL/6J or BALB/c.	No loss in striatum at 20 and 22 months (Herzig).	Decreased immobility time (bar time) at 6–19 months. Increased number of steps (drag test) at 6 –19 months. Decreased immobility time (open field) at 15 months. Increased total distance traveled (open field) at 15 months (Longo).	No synuclein pathology. Increased diastolic blood pressure (Herzig).
11	Herzig et al., 2011; Longo et al., 2014	Mouse LRRK2 Kinase Dead (D1994S) KI.	C57BL/6 or BALB/c.	Not assessed.	No changes in bar test, drag test, rotarod and open field up to 15 months (Longo).	Increased kidney weight at 6 months. Darkened kidney (Herzig).
12	Tong et al., 2009; Nichols et al., 2010; Parisiadou et al., 2014	Mouse LRRK2 R1441C KI.	C57BL/6.	No loss in SNpc or LC at 3, 12, and 22 months (Tong).	No changes in open field, rotarod and acoustic startle response. No change in AMPH injection compared (Tong).	Decreased sensitivity for firing by DA (Tong). Excess PKA activity in SPNs (Parisiadou).