General Information
Rat: Long–Evans hooded
Zinc-finger nucleases were used to create homozygous LRRK2 knock-out (KO) rats. The nucleases generated a 10 bp deletion in exon 30, which resulted in a premature stop codon.
Endogenous rat LRRK2: No
Corresponding human genotype: LRRK2 is the greatest known genetic contributor to Parkinson’s disease.
Mutated gene: LRRK2
References: Daher 2014
Additional information can be obtained on the website of the Michael J Fox Foundation for Parkinson’ disease
Transgene expression
- Absence of endogenous LRRK2 expression is confirmed in the midbrain.
Neurodegeneration
- Up to 8 months: No loss of TH-positive cells in the SN. However, LRRK2 KO rats are less affected by intra-nigral injections of LPS or alpha-synuclein-AAV.
- 12 months: No significant loss of TH positive cells in the SN.
Dopamine Homeostasis
Not reported
Inclusions
- 3-4 months: No apparent differences between nigral alpha-synuclein inclusions are observed in LRRK2 and wild-type animals injected with alpha-synuclein-AAV.
- There is no report concerning inclusions in LRRK2 KO non-injected animals.
Motor Behaviours
- 4-12 months: No significant impairment observed on the rotarod or hindlimb footplay tests compared to wild-type animals.
- 8-12 months: Increase in forelimb and hindlimb grip strength.
Response to dopaminergic treatment
- Not reported
Non-motor Behaviours
- Not reported
Electrophysiology
- Not reported
Neuroinflammation
- 3-4 months: No apparent difference in CD68 (myeloid cells) or Iba1 (microglia) immunostaining between LKKR2 KO and wild-type rats.
Updated 16/05/2018