Research Models

α-synuclein A30P/A53T Mouse (Tg)

Synonyms: hm2α-SYN-39, HM2, hm2α-SYN, human doubly mutated α-synuclein, A30P/A53T aSyn Mouse (Tg), A30P/A53T aSyn Tg Mouse (Richfield), alpha-synuclein A30P/A53T Mouse (Tg), B6J(239)

Species: Mouse
Genes: SNCA
Mutations: SNCA A30P, SNCA A53T
Modification: SNCA: Transgenic
Disease Relevance: Parkinson's Disease
Strain Name: C57BL/6J-Tg(Th-SNCA*A30P*A53T)39Eric/J
Genetic Background: Transgene injected into C57/BL6 oocytes, then bred to C57/BL6J.
Availability: Available through The Jackson Laboratory, Stock# 008239, Live.


This transgenic mouse model of Parkinson’s disease, called the HM2 model, expresses mutant human α-synuclein in dopaminergic neurons. Hemizygous mice exhibit age-related abnormalities in the dopaminergic system, including low dopamine levels and difficulties with motor coordination (Richfield et al., 2002).

The tyrosine hydroxylase (TH) promoter drives transgene expression in this model, directing expression to dopaminergic neurons. Human α-synuclein was detected in TH-positive cells in substantia nigra, ventral tegmental area, and the locus coeruleus. Human α-synuclein protein was also found in terminal projections in the striatum, nucleus accumbens, olfactory tubule, and cerebral cortex. The amount of transgenic protein in hemizygous mice is approximately half of endogenous mouse protein.

Overt loss of dopaminergic neurons has not been reported in this model, however, these mice do develop morphological abnormalities within the dopaminergic system. For example, axons in the median forebrain bundle appear dilated and have a punctate, “beaded” appearance compared to axons in non-Tg littermates.

Mutant human α-synuclein was detected in dopaminergic neurons, both cytoplasmic and nuclear. Lewy body-like inclusions are not observed in this model, at least by four months of age.

Compared with non-Tg littermates, HM2 mice exhibit an age-dependent decrease in striatal dopamine and its primary metabolites, homovanillic acid (HVA) and 3,4-dihydroxyphenyl-acetic acid (DOPAC). Measurements of all three substances were lower in HM2 mice than controls at advanced ages (13-23 months).

Behaviorally, HM2 mice showed several motor abnormalities. As young adults (two to three months), they were more active than non-Tg littermates as measured by spontaneous locomotor activity. However, by middle age (seven to nine months), they were significantly less active than non-Tg, and this difference was even greater at old age (13-23 months). In addition, old HM2 mice took significantly more time to right themselves from an inverted screen, indicating an age-dependent decrease in motor coordination.

The behavior of HM2 mice also differed from controls when challenged with repeated administration of amphetamine. Specifically, HM2 mice showed less increase in locomotor activity than non-Tg mice upon second exposure to the drug.

Modification Details

This model expresses a transgene encoding human α-synuclein with two mutations (A30P and A53T) driven by 9kb rat tyrosine hydroxylase (TH) promoter.

Related Strains

hm2αSYN-39 -B6JOla - congenic background (Prasad et al., 2011).

Phenotype Characterization

When visualized, these models will distributed over a 18 month timeline demarcated at the following intervals: 1mo, 3mo, 6mo, 9mo, 12mo, 15mo, 18mo+.


  • α-synuclein Inclusions
  • Neuronal Loss

No Data

  • Neuroinflammation
  • Mitochondrial Abnormalities
  • Cognitive Dysfunction

α-synuclein Inclusions

Inclusions were not observed at any age. Diffuse α- synuclein protein was both cytoplasmic and nuclear.


No data.

Dopamine Deficiency

Striatal dopamine concentrations were lower at all ages tested, including the earliest age, 2-3 months. Dopamine concentrations dropped with age, and levels of metabolites (e.g., DOPAC and HVA) were also lower in HM2 mice than non-Tg by 13-23 months of age.

Motor Impairment

At young age 2-3 months, HM2 mice were more active than non-Tg controls, but by middle age (7-9 months) they were less active. At advanced ages (13-23 months), they also exhibited impaired coordination as measured by the time it took to right themselves from an inverted wire screen.

Mitochondrial Abnormalities

No data.

Cognitive Dysfunction

No data.

Neuronal Loss

Not observed.


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Paper Citations

  1. . Behavioral and neurochemical effects of wild-type and mutated human alpha-synuclein in transgenic mice. Exp Neurol. 2002 May;175(1):35-48. PubMed.
  2. . Biochemical and morphological consequences of human α-synuclein expression in a mouse α-synuclein null background. Eur J Neurosci. 2011 Feb;33(4):642-56. PubMed.

External Citations

  1. The Jackson Laboratory, Stock# 008239

Further Reading

No Available Further Reading