Parkinson's Disease Models

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, 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.

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

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What our customers say:

“Robust, well-validated pre-clinical models of Parkinson's disease are a necessary tool for understanding the biology and possible treatment of this complex disease. With dedicated project management and technical support, Taconic has been a reliable partner in The Michael J. Fox Foundation's efforts to provide the research community with important, field-enabling pre-clinical models. We look forward to continuing to partner with Taconic for custom model generation projects.”
The Michael J. Fox Foundation

Surgically Induced Models of Parkinson's Disease

Unilateral 6-Hydroxydopamine Lesion of the Nigrostriatal Pathway
  • Animal models in which central dopamine neurons have been destroyed are used to study the neurodegenerative disease process associated with Parkinson's disease.
  • Administration of the neurotoxin, 6-hydroxydopamine (6-OHDA), into certain brain areas produces selective destruction of catecholamine (adrenaline, noradrenaline, and dopamine) neurotransmitter neurons.
  • The unilateral destruction of dopamine neurons causes a chemical imbalance of the brain hemispheric content of dopamine.
  • Because of this chemical imbalance or asymmetry; the administration of certain dopamine agonists, such as apomorphine, causes stimulation of intact dopamine neurons in the unaffected brain hemisphere.
  • This asymmetric stimulation is behaviorally manifested by locomotion in the direction of the unaffected hemisphere; the animal runs in circles.
  • The quantification of circling behavior can be used to access the efficacy of therapeutic agents which may be used in the treatment of Parkinson's disease.