Tg(Th-SNCA*A30P*A53T)39Eric
Transgene Detail

Summary

• Symbol: Tg(Th-SNCA*A30P*A53T)39Eric
• Name: transgene insertion 39, Eric K Richfield
• MGI ID: MGI:3530031
• Synonyms: hm²alpha-SYN-39, Tg(Th-SNCA*A30P*A53T)39Fed, Tg(Thy1-SNCA*A30P,A53T)39Fed, THsynDM
• Transgene: Tg(Th-SNCA*A30P*A53T)39Eric Location: unknown
• Alliance: Tg(Th-SNCA*A30P*A53T)39Eric page

Transgene origin

• Strain of Origin: C57BL/6

Transgene description

• Transgene Type: Transgenic (Humanized sequence, Inserted expressed sequence)
• Mutation: Insertion
• Tg(Th-SNCA*A30P*A53T)39Eric expresses 1 gene
  Transgene expresses:
  

  Organism

  Expressed Gene

  Homolog in Mouse

  Note

  human

  SNCA (6622)

  Snca	(MGI:1277151)

• Tg(Th-SNCA*A30P*A53T)39Eric expression driven by 1 gene
  Transgene expression driven by:
  

  Organism

  Driver Gene

  Homolog in Mouse

  Note

  rat

  Th (25085)

  Th	(MGI:98735)

• Mutation details: The transgene contains a 9 kb rat tyrosine hydroxylase promoter, a splice donor/intron/splice acceptor, a poly(A) site from the human growth hormone gene, and a mutated human alpha synuclein cDNA encoding a protein that carries two amino acid substitutions, Ala53Thr and Ala30Pro, which are found in human Parkinson Disease patients. RT-PCR detected transgene expression in midbrain, eye, and adrenal gland. Real time quantitative RT-PCR as well as in situ hybridization histochemistry detected high levels of transgene expression in the midbrain. Catecholaminergic nuclei in the brain of transgenic mice expressed both human mRNA and human protein. These mice express high levels of the human protein in the cell bodies of dopaminergic neurons in the midbrain and its main projection region, the striatum, dopaminergic dendrites, and nigrostriatal axons and terminals. (J:76482)

Disease models

Expression

In Structures Affected by this Mutation:

1 anatomical structure(s)

Find Mice (IMSR)

• Mouse strains and cell lines available from the International Mouse Strain Resource (IMSR)
• Carrying this Mutation: Mouse Strains: 1 strain available Cell Lines: 0 lines available

Notes

Young transgenic mice demonstrated significantly increased locomotor activity and a shorter time to right compared to both nontransgenic littermates and Tg(SNCA)5Fed transgenic mice, which express the wild-type human gene under control of a 9 kb rat Thy1 promoter. Locomotor responses to amphetamine were impaired in young transgenic mice. The abnormal axons visualized in the median forebrain bundle of transgenic mice were more dilated and beaded in appearance compared to those seen in nontransgenic littermate controls. The terminals in the nucleus accumbens of transgenic mice also appeared abnormal with the smaller caliber processes and terminals often dilated or enlarged compared to those seen in nontransgenic littermate controls. Neither compact round cytoplasmic inclusions nor intranuclear inclusions were identified in transgenic mice at 4 months of age. J). Axons in transgenic mice that stained for Thy1 were beaded and dilated in appearance and displayed increased discontinuities.

References

• Original: J:76482 Richfield EK, et al., Behavioral and neurochemical effects of wild-type and mutated human alpha-synuclein in transgenic mice. Exp Neurol. 2002 May;175(1):35-48
• All: 17 reference(s)