The Human LRRK2 G2019S Targeted Replacement MouseModel 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, allowing generation of a LRRK2 gene constitutive KO model upon intercrossing with a Cre-deleter strain.
- 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.