B6.Cg-Snca^tm1Rosl Tg(SNCA*A30P)192Rwm/J

Stock number: 024338
Product name: SNCA-A30P+ Snca-/-
Research areas: Neurobiology Research, Research Tools

Description

These SNCA-A30P mice express a transgene containing a mutant human SNCA gene and are suitable for use in applications related to the study of Parkinson's disease.

Detailed description

The A30P mutation of the human SNCA gene has been linked to familial Parkinson’s disease. These mutant mice carry a transgene containing a human SNCA gene with the A30P mutation and a knock out allele of the mouse Snca gene. Western blot analysis of brain tissue reveals human α-synuclein protein at levels significantly lower than endogenous wildtype C57BL/6 mouse α-synuclein protein levels. The transgene expression pattern is similar to the endogenous mouse Snca expression pattern. The transgene was detected at a single site of integration near the telomere on one copy of chromosome 15 by fluorescence in situ hybridization analysis. Electrically evoked dopamine release is reduced in the striatal caudate putamen, but not in the nucleus accumbens, of SNCA-A30P mice, when compared to Snca KO mice. Mutant mice exhibit increased anxiety with age and an increase in activity during the dark phase of a 12 hour- 12 hour light-dark cycle. Mice that are homozygous for the targeted mutation and hemizygous for the transgene are viable and fertile. The Donating Investigator has not attempted to make the strain homozygous for the transgene but reports double homozygous animals should be viable.

Development

A BAC construct carrying the complete 111-kb human SNCA locus containing the A30P point mutation was microinjected into the pronucleus of C57BL/6 fertilized eggs. This transgene consists of a 135 kb BAC clone, PAC-27 M07, containing the complete 111 kb human SNCA genomic DNA locus with the Parkinson disease-associated A30P mutation, flanked by 18 kb of 5' and 6 kb of 3' genomic DNA sequence which includes the promoter. Founder line 192 was subsequently crossed to mice carrying the Snca^tm1Rosl allele (see, for example, Stock No. 003692) on a congenic C57BL/6 background for at least 6 generations. The transgene was detected at a single site of integration near the telomere on one copy of chromosome 15 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
Marker symbol: Snca
Marker name: synuclein, alpha
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*A30P)192Rwm
Name: transgene insertion 192, Richard Wade-Martins
MGI accession ID: MGI:5543905
Generation method: Transgenic
Attributes: Inserted expressed sequence; Humanized sequence
Marker symbol: Tg(SNCA*A30P)192Rwm
Marker name: transgene insertion 192, Richard Wade-Martins
Chromosome: 15
Strain of origin: C57BL/6
Expressed genes: SNCA,synuclein alpha,human
Molecular note: This transgene consists of a 135 kb BAC clone, PAC-27 M07, containing the complete 111 kb human SNCA genomic DNA locus with the Parkinson Disease-associated A30P mutation, flanked by 18 kb of 5' and 6 kb of 3' genomic DNA sequence which includes the promoter. Western blot analysis confirmed expression of the human protein in the brain. Line 192 contains a single copy insertion in chromosome 15.