The Rab29 Overexpression Mouse

Model 16552 is a constitutive knock-in of murine Rab29 under control of the Pgk promoter generated by targeted transgenesis into the ROSA26 locus.

• Rab29 is a Rab GTPase that acts as a key regulator in vesicle trafficking and maintaining the endosome-trans-Golgi network structure. Rab29, together with LRRK2, plays a role in the retrograde trafficking pathway for recycling proteins.
• Rab29 is one of five genes located within the PARK 16 locus that has been linked to Parkinson's disease.
• Rab 29 is a direct substrate of LRRK2 — a kinase protein in which autosomal dominant missense mutations are linked to Parkinson's disease through increased kinase activity. In addition, Rab29 is a regulator of LRRK2, controlling its localization and activation.
• There is a substantial increase in Rab29 protein levels by western blot in brain, kidney, and distal colon, with a moderate increase in spleen, lungs, macrophages.

The Human LRRK2 G2019S Targeted Replacement Mouse

Model 13940 has the human G2019S point mutation introduced into exon 41 of the mouse LRRK2 gene. Additionally, exon 41 is flanked by lox P sites, potentially allowing generation of a LRRK2 gene constitutive KO model upon intercrossing with a Cre-deleter strain. See model page for more information.

• The G2019S alpha-mutation is linked to the development of Parkinson's disease, both sporadic and familial.
• In patients, the G2019S LRRK2 mutation is an autosomal dominant mutation that leads to pathology similar to what is observed with idiopathic Parkinson's disease.
• At 18 months of age, LRRK2 G2019S mice show an increased locomotor response after amphetamine challenge.
• This knock-in mutation does not appear to affect basal motor function or more complex behavior in C57Bl6 mice.

The Michael J Fox Foundation Sponsored Rats for Parkinson's Research

The loss of nigrostriatal dopamine neurons and reduced motor abilities are consequences of Parkinson's Disease. Mutations in the LRRK2 and alpha synuclein (SNCA) genes are associated with familial Parkinson's disease and affect the nigrostriatal pathway.

The rat as an experimental organism can offer some unique strengths compared to mice:

• rats can perform more sophisticated behavioral tasks,
• are better suited for electrophysiological multichannel recordings, and
• the nigrostriatal circuit of the rat is more sensitive to insults than that of mice.