TABLE 1.

Mouse LRRK2 KO models.

Mouse LRRK2 KO models	Author(s), year(s)	Model	Background (strain)	DA neuronal loss	Locomotor/behavioral changes	Other notes
1	Giaime et al., 2017	Double KO of LRRK1 and LRRK2 KO mouse [mouse LRRK2 (−/−)/mouse LRRK1 (−/−)].	Mouse C57BL/6J and 129 hybrid.	Loss at 14–15 months in SNpc and LC. Loss of medium spiny neurons in striatum.	Not assessed.	Presence of synuclein pathology. Increased p62 and LC3 in brain at 15 months. Increased electron dense vacuoles in SNpc at 10 months.
2	Dächsel et al., 2010; Hinkle et al., 2012; Volta et al., 2015	LRRK2 KO by removal of exon 41 of LRRK2 [mouse LRRK2 (−/−)].	C57BL/6J [(also contains C57BL/6N – (Yue et al., 2015)]	No loss in SN at 18 months (Hinkle).	Increased thigmotaxis (open field), decreased center exploration time (open field) and decreased object approaches (novel object test) at 7 and 16 months. Increased latency to fall (rotarod) at 7 months (Hinkle).	No synuclein or tau pathology in kidney or brain at 3, 12, and 18 months. Progressive kidney degeneration seen at 3 months with increased lipofuscin or lysosomes. Increased autophagy markers at 20 months (p62 at 12 months) (Hinkle). Increased neurite outgrowth in hippocampal and midbrain neuron cultures (Dächsel).
3	Herzig et al., 2011	LRRK2 KO using cre-recombinase deletion [mouse LRRK2 (−/−)].	C57BL/6J or BALB/c.	Not assessed.	Not assessed.	Darkened kidney. Increased weight and vacuoles at 5 months. Increase of secondary lysosomes in the kidney and lung cells at 1.5 months. Increased diastolic blood pressure.
4	Tong et al., 2010a, 2012	LRRK2 KO by deletion of promoter and exon 1 [mouse LRRK2 (−/−)].	C57BL/6J and 129 hybrid.	No loss up to 24 months.	Not assessed.	Smaller size, increased synuclein aggregation, increased p62, increased LC3-I, decreased LC3-II, and increased apoptosis in the kidneys at 20 months (Tong et al., 2010a). Increased weight (kidney/body weight) and size of kidney at 1, 4, and 7 months. Decreased HMW α-synuclein, decreased LC3-I, and decreased p62 at 7 months. Increased kidney injury molecule-1 and cathepsins (Tong et al., 2012).
5	Andres-Mateos et al., 2009	LRRK2 KO by partial deletion of exon 39, complete deletion of exon 40 and insertion of premature stop codon [mouse LRRK2 (−/−)].	C57BL/6.	No loss in SN up to 18–22 months.	Not assessed.	Lack of sensitivity to MPTP.
6	Lin et al., 2009; Parisiadou et al., 2009	LRRK2 KO by deletion of exon 2 resulting in premature stop codon in exon 3 [mouse LRRK2 (−/−)].	C57BL/6J.	No obvious degeneration (not directly assessed).	No changes in open field and rotarod (Lin).	Protection against α-synuclein aggregation in the striatum (Lin).