LRRK2-KO-Rat

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