TABLE 5.
Rat transgenic LRRK2 models.
Author(s), year(s) | Model (species, gene, mutation, tag) | Background (strain) | Type of expression system | DA neuronal loss | Locomotor/behavioral changes | |
Transgenic overexpression cDNA rat models | ||||||
1 | Zhou et al., 2009, 2011 | Human LRRK2 WT – HA. | Sprague-Dawley. | Tet-inducible OE of human LRRK2 WT with a ubiquitous promoter (TRE-miniCMV). | Not assessed. | Not assessed. |
2 | Zhou et al., 2011 | Human LRRK2 G2019S – HA. | Sprague-Dawley. | Tet-inducible OE of human LRRK2 G2019S with a ubiquitous promoter (TRE-miniCMV). | No loss in SNpc and LC at 18 months (compared to “tet-only” instead of non-transgenic). | Increased total distance (open field) at 18 months using temporary expression model (given doxycycline until 5 months). |
Transgenic overexpression BAC rat models | ||||||
1 | Sloan et al., 2016 | Human LRRK2 WT – YPet. | Sprague-Dawley. | OE of human LRRK2 WT with BAC. | Not assessed. | No changes in rotarod, T-maze, or grip strength test. |
2 | Sloan et al., 2016 | Human LRRK2 G2019S – YPet. | Sprague-Dawley. | OE of human LRRK2 G2019S with BAC. | No loss in SN at 18–21 months. | Decreased latency to fall at 3–6 and 18–21 months. Decreased alternations in T-maze at 18–21 months. |
3 | Sloan et al., 2016 | Human LRRK2 R1441C – Ypet. | Sprague-Dawley. | OE of human LRRK2 R1441C with BAC. | No loss in SN at 18–21 months. | Decreased latency to fall, decreased alternations (T-maze) and increased gait disturbances at 18–21 months. |
4 | (Shaikh et al., 2015) (Taconic – Dr. Chenjian Li) | Human LRRK2 R1441G. | Sprague-Dawley. | OE of human LRRK2 R1441G under BAC. | No loss in SN or striatum up to 9 months. | No changes in forelimb placing test, adjusting steps test, footprint analysis, open field test, acoustic startle response and Morris water maze. |
5 | (Walker et al., 2014; West et al., 2014; Daher et al., 2015; Lee et al., 2015; Volpicelli-Daley et al., 2016) (Taconic – Dr. Chenjian Li) | Human LRRK2 G2019S. | Sprague-Dawley. | OE of human LRRK2 G2019S under BAC (MJ Farrer Lab). | No changes (Daher). | Decreased latency to fall on rotarod at 6 months. No difference in cylinder and beam walking test (Walker). Postural instability at 8 months but was recovered at 12 months. Rearings increased at 12 months (Lee). |