TABLE 3.

Transgenic OE of LRRK2 using cDNA in mouse models.

Transgenic overexpression cDNA Mouse Models	Author(s), year(s)	Model (species, gene, WT or mutant, tag)	Background (strain)	Type of expression system	DA neuronal loss	Locomotor/behavioral changes
1	Xiong et al., 2018	Human LRRK2 G2019S – TAP.	C57BL/6 (backcrossed).	Tet-inducible OE of human LRRK2 G2019S with human TH promoter (catecholaminergic cell specific).	Loss at 15 months in SNpc and 24 months in LC.	Decreased stride length and increased descending time on the pole test at 24 months. Normal rotarod and open field.
2	Xiong et al., 2018	Human LRRK2 GS/Kinase Dead (G2019S + D1994A) – TAP.	C57BL/6 (backcrossed).	Tet-inducible OE of human LRRK2 kinase dead with human TH promoter (catecholaminergic cell specific).	No loss in SNpc or LC up to 25 months.	No changes on rotarod, open-field, pole test, and gait analysis.
3	Weng et al., 2016	Human LRRK2 R1441C – HA.	FVB/N.	OE of human LRRK2 R1441C under CMVE/(PDGF)-β promoter (neuronal transgene specific).	Loss in SNpc at 16 months. No neuronal loss in striatum up to 16 months.	Decreased velocity, distance moved and rearings starting at 16 months.
4	Liu et al., 2015	Human LRRK2 WT – HA.	C57BL/6J.	Tet-inducible OE of human LRRK2 WT with PITX3 promoter (DA midbrain neuron specific).	No loss in SNpc or VTA up to 20 months.	No changes in open field, rotarod, and gait analysis up to 18 months.
5	Liu et al., 2015	Human LRRK2 G2019S – HA.	C57BL/6J	Tet-inducible OE of human LRRK2 G2019S LRRK2 with PITX3 promoter (DA midbrain neuron specific).	No loss in SNpc or VTA up to 20 months.	No changes in gait analysis, rotarod, fine movement and horizontal/vertical movement.
6	(Garcia-Miralles et al., 2015) [Note: (Herzig et al., 2012) developed a similar model]	Human LRRK2 WT.	C57BL/6.	OE of human LRRK2 WT with murine Thy1.2 promotor (neuronal transgene specific).	No loss in SNpc up to 12–13 months (limited expression in SNpc).	Not assessed.
7	(Garcia-Miralles et al., 2015) [Note: (Herzig et al., 2012) developed a similar model]	Human LRRK2 G2019S.	C57BL/6.	OE of human LRRK2 G2019S with murine Thy1.2 promoter (neuronal transgene specific).	No loss in SNpc up to 12–13 months (limited expression in SNpc).	Not assessed.
8	Tsika et al., 2014	Human LRRK2 R1441C.	C57BL/6J.	Conditional (Cre-dependent) OE of human LRRK2 R1441C with murine ROSA26 promoter (crossed with DAT-Cre for central DAT-positive midbrain neuron expression).	No loss in SNpc up to 22 months.	No changes in open field, rotarod or olfactory sense at 19–20 months.
9	Maekawa et al., 2012	Human LRRK2 I2020T – V5.	C57BL/6J (backcrossed).	OE of human LRRK2 I2020T with CMV promoter (whole body expression).	No loss in SNc up to 18 months.	Increased slips on beam test (23 weeks), decreased latency to fall time (34 weeks), and increased rearings (22 weeks).
10	Chen et al., 2012; Weng et al., 2016	Human LRRK2 WT – HA.	FVB/N.	OE of human LRRK2 WT with CMVE/(PDGF)-β promoter (neuronal transgene specific).	No loss in SNpc. No neuronal loss in striatum, cerebral cortex, or hippocampus.	No changes in open field and pole test.
11	Chen et al., 2012; Chou et al., 2014	Human LRRK2 G2019S – HA.	FVB/N.	OE of human LRRK2 G2019S with CMVE/(PDGF)-β promoter (neuronal transgene specific).	Loss in SNpc starting at 12 months (50%). No neuronal loss seen in striatum, cerebral cortex, or hippocampus (Chen). No loss at 8–9 months in SNpc (Chou).	Decreased ambulatory movement, distance moved, and increased time on pole test at 12 months (Chen). Decreased ambulatory movement at 8–9 months (Chou).
12	Herzig et al., 2012	Human LRRK2 WT.	C57BL/6	OE of human LRRK2 WT with murine Thy1 promoter (neuronal transgene specific).	Not assessed (limited expression in SNpc).	Trend for increased rotarod and distance traveled, but not significant (data not shown).
13	Herzig et al., 2012	Human LRRK2 G2019S.	C57BL/6.	OE of human LRRK2 G2019S with murine Thy1 promoter (neuronal transgene specific).	No obvious pathology up to 19 months due to lack of expression in SN (data not shown).	Increased rotarod performance at 3–4 months and increased distance traveled in first 30 min at 7 months (males only). These effects waned later in age (data not shown for rotarod).
14	Ramonet et al., 2011	Human LRRK2 WT.	C57BL/6J (backcrossed).	OE of human LRRK2 WT with CMVE/human (PDGF)-β promoter (neuronal transgene specific).	Not assessed (limited expression in SNpc).	Not assessed.
15	Ramonet et al., 2011	Human LRRK2 R1441C.	C57BL/6J (backcrossed).	OE of human LRRK2 R1441C with CMVE/human (PDGF)-β promoter (neuronal transgene specific).	Not assessed (limited expression in SNpc).	Decreased horizontal and vertical activity measured by beam breaks at 15 months.
16	Ramonet et al., 2011; Lim et al., 2018	Human LRRK2 G2019S.	C57BL/6J (backcrossed).	OE of human LRRK2 G2019S with CMVE/human (PDGF)-β promoter (neuronal transgene specific).	Loss in SNpc at 19–20 months (17–18%). No loss in VTA at 19–21 months (Ramonet).	No changes in open field, beam test or acoustic startle response up to 15 months (Ramonet). Decreased latency to fall time on rotarod at 65–83 weeks and Increased anxiety/depression 43–52 weeks (Lim).
17	Lin et al., 2009	Human LRRK2 WT – HA.	C57BL/6J.	Tet-inducible OE of human LRRK2 WT with CaMKII promoter (neuron specific).	Not assessed.	No changes in beam breaks and latency to fall up to 6 months (Lin).
18	Wang L. et al., 2008; Lin et al., 2009	Human LRRK2 G2019S – HA.	C57BL/6J.	Tet-inducible OE of human LRRK2 G2019S with CaMKII promoter (neuron specific).	Not assessed in SNpc (limited expression). No neuronal loss in striatum or cortex up to 20 months (Lin).	Increased beam breaks at 12 and 18 months. Rearings normal up to 18 months (Lin).
19	Lin et al., 2009	Human LRRK2 kinase domain deletion – HA.	C57BL/6J.	Tet-inducible OE of human LRRK2 kinase domain deletion with CaMKII promoter (neuron specific).	Not assessed.	Not assessed.