B6(Cg)-Snca^tm1.1Vlb/J

Stock number: 025636
Product name: SNCAflox delta neo
Research areas: Neurobiology Research, Research Tools

Description

These floxed mutant mice possess loxP sites flanking the first coding exon of the Snca gene. This strain may be useful for generating conditional mutations in applications related to neurodegenerative synucleinopathies, such as Parkinson's disease and multiple system atrophy.

Detailed description

These Snca flox delta neo mice possess loxP sites on either side of the first coding exon (exon II) of the targeted gene. When these mutant mice are bred to mice that express Cre recombinase, resulting offspring will have the first coding exon deleted in the cre-expressing tissues. Removal of the floxed sequence creates a null allele. Mice that are homozygous for this allele are viable and fertile. The Donating Investigator reports that Western blot analysis of total protein extracts from several regions of the brain indicate that expression of the targeted mutation allele is similar to that observed in wildtype mice.

When crossed with transgenic mice expressing Cre recombinase under the control of the actin promoter, no expression of alpha-synuclein protein was detected in the resulting mice by Western blot analysis.



Mutations in human SNCA that result in aberrant polymerization and fibrillar aggregations are associated with neurodegenerative synucleinopathies, such as Parkinson's disease and multiple system atrophy.

Development

A targeting vector containing a FRT site-flanked NEO cassette and a loxP site was inserted downstream of exon II (the first coding exon) of the targeted Snca gene, and another loxP site was inserted upstream of exon II. This construct was electroporated into C57BL/6N-A^tm1Brd-derived JM8A3.N1 embryonic stem (ES) cells. The resulting chimeric animals were bred to C57BL/6J mice for 2 generations and then crossed to transgenic mice (on a congenic C57BL/6 genetic background) expressing FLP recombinase under the control of the human ACTB promoter. The FLP recombinase mediated excision of the FRT flanked NEO cassette and a 400 bp fragment encompassing a simple repeat region, which does not affect Snca locus expression. Snca flox delta neo mice that retained the floxed exon II were then bred to C57BL/6J mice for 2 generations to remove the FLP recombinase transgene. Heterozygotes were crossed to generate homozygotes. 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^tm1.1Vlb
Name: targeted mutation 1.1, Vladimir L Buchman
MGI accession ID: MGI:5614654
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Marker symbol: Snca
Marker name: synuclein, alpha
Chromosome: 6
Strain of origin: C57BL/6N-A^tm1Brd
Molecular note: A targeting vector containing a FRT site-flanked neo cassette and a loxP site was inserted downstream of exon 2 (the first coding exon) of the targeted gene, and another loxP site was inserted upstream of exon 2. Flp-mediated recombination removed the FRT-flanked neo cassette leaving exon 2 floxed.