B6.Cg-Tg(SNCA)OVX37Rwm Snca^tm1Rosl/J

Stock number: 023837
Product name: SNCA-OVX
Research areas: Neurobiology Research, Research Tools

Description

These SNCA-OVX mice express a transgene containing the human SNCA gene and develop age-dependent motor incoordination and loss of nigrostriatal dopamine neurons. They are suitable for use in applications related to the study of Parkinson disease.

Detailed description

These mutant mice carry a transgene containing human SNCA gene and a knock out allele of the mouse Snca gene. Human α-synuclein protein levels in the striatum of mutant mice is 1.9-fold higher than levels of endogenous mouse α-synuclein protein. Transgene expression is detected in the striatum (caudate putamen and nucleus accumbens). Mice that are homozygous for the targeted mutation and the transgene are viable and fertile. Male mice have an increased dry stool weight. SNCA-OVX mice, aged 18 months, exhibit age-related impairment of motor coordination, and loss of nigrostriatal dopamine neurons. Diminishment of motor coordination and firing rate of dopamine neurons of the substantia nigra pars compacta is age-dependent. Dopamine transmission in the dorsal striatum is reduced as early as 3-4 months of age. The transgene was detected at a single site of integration near the centromere of chromosome 4 by fluorescence in situ hybridization analysis.

Development

A BAC construct carrying the complete 111-kb human wildtype SNCA locus and endogenous promoter sequences was microinjected into the pronucleus of CBA X C57BL/6 F1 fertilized eggs. Founder line 37 was subsequently crossed to mice carrying the Snca^tm1Rosl allele (see, for example, Stock No. 003692) on a congenic C57BL/6 background for 9 generations. The transgene was detected at a single site of integration near the centromere of chromosome 4 by fluorescence in situ hybridization analysis. Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6J (Stock No. 000664) at least once to establish the colony.

Allele

Symbol: Snca^tm1Rosl
Name: targeted mutation 1, Arnon Rosenthal
MGI accession ID: MGI:1888382
Generation method: Targeted
Attributes: Null/Knockout
Synonyms: alpha-Syn^-; alpha-Synko
Marker symbol: Snca
Marker name: synuclein, alpha
Marker synonyms: alphaSYN; alpha-Syn; alpha-synuclein; NACP; PARK1; PARK4; PD1
Chromosome: 6
Strain of origin: 129X1/SvJ
Molecular note: A PGK-neo cassette was used to delete exons 1 and 2, encoding amino acids 1 through 41 as well as a 5' untranslated region. RT-PCR analysis of extracts from the brains of homozygous mutant mice, using probes for both the deleted 5' region as well the untargeted 3' region, showed an absence of transcript. Western blot analysis, immunohistochemical analysis, and in situ hybridization confirmed a lack of encoded protein in homozygous mutant mice.

Allele

Symbol: Tg(SNCA)OVX37Rwm
Name: transgene insertion OVX37, Richard Wade-Martins
MGI accession ID: MGI:5544307
Generation method: Transgenic
Attributes: Inserted expressed sequence; Humanized sequence
Synonyms: SNCA-OVX
Marker symbol: Tg(SNCA)OVX37Rwm
Marker name: transgene insertion OVX37, Richard Wade-Martins
Marker synonyms: SNCA-OVX
Chromosome: 4
Strain of origin: (CBA x C57BL/6)F1
Expressed genes: SNCA,synuclein alpha,human
Site of expression: Transgene expression is detected in the striatum (caudate putamen and nucleus accumbens).
Molecular note: This transgene consists of a BAC carrying the complete 111-kb wild-type human SNCA locus. This line overexpresses the human protein at nearly twice the endogenous level of the mouse protein. Fluorescence in situ hybridization analysis identified a single site of integration near the centromere of chromosome 4.