TH-hsynwt – Mouse

General Information

Mouse: Swiss Webster x CB57BL/DAB, CB57BL/J6 or CB57BL/J6 x CB57BL/6JOIa

Expression of the wild type human alpha-synuclein under the control of the rat tyrosine hydroxylase (TH) promoter.

Endogenous mouse alpha synuclein:

  • Yes (Swiss Webster x CB57BL/DAB and CB57BL/J6)
  • No (CB57BL/J6 x CB57BL/6JOIa). CB57BL/6JOIa mice have a spontaneous deletion of the alpha-synuclein gene.

Corresponding human genotype: gene multiplication in familial PD; polymorphism in the noncoding region of the alpha-synuclein locus

Transgene insertion:  not specified

References: Matsuoka 2001; Richfield 2002;Manning-Bog 2003; Su 2008; Prasad 2011

Transgene expression

Swiss Webster x CB57BL/DAB

  • 12 months: Transgene expression is observed in the brainstem and midbrain neurons, olfactory bulb and retinal anacrine cells. High protein levels are detected in nigrostriatal dopamine neurons.

CB57BL/J6

  • 2-3 months: high transgene expression is observed in the SN (cell bodies) and striatum (terminals), eye, locus coeruleus. Expression of human alpha-synuclein is about 25% of that of endogenous mouse alpha-synuclein.

CB57BL/J6 x CB57BL/6JOIa

  • Low expression of human alpha-synuclein is observed in the striatum; these levels do not reach that normally observed for the endogenous mouse alpha synuclein in the CB57BL/J6 background.

Neurodegeneration

Swiss Webster x CB57BL/DAB

  • 12 months: No loss of TH-positive neurons is observed. Reduced sensitivity to paraquat toxicity detected.

CB57BL/J6

  • 2-3 months: No loss of TH-positive neurons is detected but an increase in DAT density is observed. Increased vulnerability to MPTP treatment is observed.
  • 19 months: Slight loss (13%) of TH-positive neurons is observed compared to non-transgenic mice

CB57BL/J6 x CB57BL/6JOIa

  • Elevated basal expression of striatal tyrosine hydroxyls is observed compared to that detected in non-transgenic mice.
  • 9 months: no changes in the number and size of TH-positive neurons is observed in the SN

Dopamine Homeostasis

Swiss Webster x CB57BL/DAB

  • Not reported

CB57BL/J6

  • No changes in dopamine and dopamine metabolites are detected

CB57BL/J6 x CB57BL/6JOIa

  • Increased levels of striatal catecholamine and catecholamine metabolites are detected.

Inclusions

Swiss Webster x CB57BL/DAB

  • 12 months: no inclusions are detected

CB57BL/J6

  • 2-3 months: no inclusions are observed

CB57BL/J6 x CB57BL/6JOIa

  • Inclusions are detected in the hippocampus (DG)

Motor Behaviours

Swiss Webster x CB57BL/DAB

  • Not reported

CB57BL/J6

  • 2-3 months: Increased motor response (horizontal activity) to repeated amphetamine injection is detected. A greater decrease in motor activity following MPTP treatment is observed in the transgenic mice compared to non-transgenic littermates.
  • Up to 23 months: No significant differences are observed in spontaneous locomotor activities at any age compared to nontransgenic mice although an overall age-related decline is observed.

CB57BL/J6 x CB57BL/6JOIa

  • Not reported

Response to L-DOPA treatment

Swiss Webster x CB57BL/DAB

  • Not reported

CB57BL/J6

  • Not reported

CB57BL/J6 x CB57BL/6JOIa

  • Not reported

Non motor Behaviours

Swiss Webster x CB57BL/DAB

  • Not reported

CB57BL/J6

  • Not reported

CB57BL/J6 x CB57BL/6JOIa

Not reported

Electrophysiology

Swiss Webster x CB57BL/DAB

  • Not reported

CB57BL/J6

  • Not reported

CB57BL/J6 x CB57BL/6JOIa

  • Not reported

Neuroinflammation

Swiss Webster x CB57BL/DAB

  • Not reported

CB57BL/J6

  • 1 months: increased number of activated microglia is observed in the SN but not in the striatum. An elevation of TNF-alpha expression is detected

CB57BL/J6 x CB57BL/6JOIa

  • Not reported

 

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