These hwα-SYN-5 mice express wildtype human alpha-synuclein (hα-SYN) under the control of the rat tyrosine hydroxylase promoter. Expression of hα-SYN is detected in cell bodies, axons, and terminals of the nigrostriatal system (mRNA expression in midbrain, eye, and adrenal gland, with high levels of protein expression in the cell bodies of dopaminergic neurons in the midbrain and striatum). Hemizygous mice exhibit several Parkinson's disease-related characteristics including increased density of the dopamine transporter, impairments of the ubiquitin-proteasome system, and age-related progressive loss of locomotor activity and substantia nigra pars compacta dopaminergic neurons. The Parkinson's disease-related phenotype of these hwα-SYN-5 mice is intermediate between that of the C57BL/6J wild-type controls and the severely affected hm2α-SYN-39 strain (see Stock No. 008239). As such, these hwα-SYN-5 transgenic mice may be useful for studying Parkinson's disease, Lewy bodies, neurodegeneration, and synaptic plasticity in conjunction with Stock No. 008239.
A 469 bp human alpha-synuclein cDNA was placed downstream of a 9 kb rat tyrosine hydroxylase promoter (and splice donor/intron/splice acceptor) and upstream of a polyA signal. This transgene was injected into C57BL/6 oocytes. Mice from founder line 5 (hwα-SYN-5) were found to have the highest levels of transgene mRNA expression in midbrain. These hwα-SYN-5 mice were maintained by breeding transgenic mice with wild-type or C57BL/6J for many generations prior to sending to The Jackson Laboratory Repository. Upon arrival, mice were bred to C57BL/6J (Stock No. 000664) for at least one generation to establish the colony.
|Expressed Gene||SNCA, synuclein alpha, human|
|Site of Expression|
|Allele Name||transgene insertion 5, Eric K Richfield|
|Allele Type||Transgenic (Inserted expressed sequence, Humanized sequence)|
|Allele Synonym(s)||hwalpha-SYN-5; Tg(Th-SNCA)5Fed; THsynWT|
|Gene Symbol and Name||Tg(Th-SNCA)5Eric, transgene insertion 5, Eric K Richfield|
|Promoter||Th, tyrosine hydroxylase, rat|
|Expressed Gene||SNCA, synuclein alpha, human|
|Strain of Origin||C57BL/6|
|General Note||Line 88 was also generated using this wild-type construct.|
|Molecular Note||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 wild-type human alpha synuclein cDNA. 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.|
|Mutations Made By|| |
Eric Richfield, Rutger's University (EOHSI/UMDNJ)
When maintaining a live colony, hemizygotes are bred to wildtype siblings or to inbred C57BL/6J mice.
When using the C57BL/6J-Tg(Th-SNCA)5Eric/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #008245 in your Materials and Methods section.
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