TABLE 4.
Transgenic OE of LRRK2 using BAC in mouse models.
Transgenic overexpression BAC 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 | Beccano-Kelly et al., 2015; Volta et al., 2015 | Human LRRK2 WT. | C57BL/6J [backcrossed from Melrose et al. (2010) by Beccano-Kelly]. | OE of human LRRK2 WT using BAC (RP-11 568G5). | Not assessed. | Decreased total distance, ambulatory time and rearings at 3–6 months (Beccano-Kelly). Decreased rearings at 12 months (Volta). |
2 | Volta et al., 2015 | Human LRRK2 G2019S. | C57BL/6J [backcrossed from Melrose et al. (2010)]. | OE of human LRRK2 G2019S using BAC (RP-11 568G5). | Not assessed. | Increased cylinder rearings at 6 months, but normal at 12 months. |
3 | Dächsel et al., 2010; Melrose et al., 2010 | Human LRRK2 WT. | FVB/N (backcrossed – Melrose). | OE of human LRRK2 WT using BAC (RP-11 568G5). | No loss in SN up to 22–24 months (Melrose). | No changes in open field, beam-crossing test, gait footprint analysis inked footprint analysis or negative geotaxis test at 7–8 months (Melrose). |
4 | Dächsel et al., 2010; Melrose et al., 2010 | Human LRRK2 G2019S. | FVB/N (backcrossed). | OE of human LRRK2 G2019S using BAC (RP-11 568G5). | No loss in SN up to 22–24 months (Melrose). | Increased mean path length and thigmotaxis (wall hugging) in open field at 7–8 months. No other changes in beam-crossing, gait footprint analysis or negative geotaxis tests (Melrose). |
5 | Dächsel et al., 2010 | Human LRRK2 Y1699C. | FVB/N (backcrossed). | OE of human LRRK2 Y1699C using BAC (RP-11 568G5). | Not assessed. | Not assessed. |
6 | Li et al., 2007, 2010 | Mouse LRRK2 WT – FLAG. | C57BL/6J. | OE of mouse LRRK2 WT using BAC (RP23-312I9). | No loss in SNpc at 12 months (2010). | Increased rearings at 6 and 12 months, total distance at 12 months and total move time at 12 months. Decreased slips/step at 12 months (2010). |
7 | Li et al., 2010 | Mouse LRRK2 G2019S – FLAG. | C57BL/6J. | OE of mouse LRRK2 G2019S with mouse BAC (RP23-312I9). | No loss in SNpc at 12 months. | No changes in open field test, beam test, and gait stride test at 12 months. |
8 | Li et al., 2009 | Human LRRK2 WT. | FVB/NJ. | OE of human LRRK2 WT with BAC. | No loss up to 9–10 months. | No changes in open field or cylinder test. |
9 | Li et al., 2009; Bichler et al., 2013; Dranka et al., 2013 | Human LRRK2 R1441G. | FVB/NJ. | OE of human LRRK2 R1441G with human BAC (RP135). | No loss up to 9–10 months (Li). | Decreased rearings at 6 and 10–12 months (Li). Decreased rearings (cylinder), center activity (open field), and horizontal activity (open field) at 20 months (Bichler) (See Bichler for other important negative data). Decreased latency to fall and increased time on pole test at 16 months (Dranka). |