C57BL/6-Tg(Thy1-SNCA*)G51DNuber/J

Stock number: 039402
Product name: Thy1-G51D, G51D, 1D

Research areas: Neurobiology Research

Description

Thy1-G51D (G51D, 1D) transgenic mice express human αS (synuclein, alpha; SNCA) cDNA modified with the G51D mutation from the mouse neuron-specific thymus cell antigen 1, theta (Thy1) promoter. A model familial Parkinson's disease (fPD), these mice are useful for studies of neuronal SNCA toxicity associated with bradykinetic motor phenotypes.

Detailed description

Cytoplasmic αS (synuclein, alpha; SNCA) deposits, including Lewy bodies and Lewy neurites, are defining lesions in Parkinson's disease (PD) brain. A strong genetic association exists between early onset familial forms of PD (fPD) and various αS mutations that are collectively localized in the membrane-binding N-terminal region. In humans, the G51D αS mutation causes an early onset PD which responds to L-DOPA but rapidly progresses to severe phenotypes including dyskinesias, dementia, limb myoclonus, and seizures.

Thy1-G51D (G51D, 1D) mice express human SNCA cDNA modified with the G51D mutation from the mouse neuron-specific thymus cell antigen 1, theta (Thy1) promoter. The SNCA protein contains six to nine imperfect 11-residue repeats with the core consensus sequence KTKEGV and adopts a helical conformation on binding to lipid membranes. G51D introduces a negative charge in a hydrophobic stretch presumed to be embedded in the outer leaflet of vesicle membranes. Moderately high overexpression of mutant SNCA (~2-3 fold) is reported in 1D homozygotes.

Development

Full-length human SCNA cDNA was mutagenized to carry a G51D mutation (nucleotide change: GGT to GAT in exon 3) and placed under the control of the mouse Thy1 neuronal promoter. The transgenic vector was introduced to C57BL/6J embryos. The donating laboratory reported the resultant mice were maintained on a C57BL/6J genetic background prior to sending to The Jackson Laboratory in 2024 (see SNP results). Moderately high overexpression of SNCA (~2-3 fold) is reported in homozygotes. Upon arrival, sperm was cryopreserved. If rederiving a live colony, we will use an aliquot of frozen sperm to fertilize C57BL/6NJ oocytes (Stock No. 005304).

In 2024, a 48 SNP (single nucleotide polymorphism) panel analysis, with 43 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the males sent to The Jackson Laboratory Repository. While the 43 markers throughout the genome suggested a C57BL/6 genetic background, 4 of 5 markers that determine C57BL/6J from C57BL/6N were found to be homozygous C57BL/6N allele-type (chromosomes 1 [~139 Mbp], 8 [~58 Mbp], 15 [~57 Mbp], 19 [~50 Mbp]) with 1 of 5 as heterozygous C57BL/6N allele-type (chromosome 6 [~108 Mbp]). These data suggest that the mice sent to The Jackson Laboratory were on a mixed C57BL/6J;C57BL/6N genetic background (majority C57BL/6N).

Allele

Symbol: Tg(Thy1-SNCA*)G51DNuber
Name: transgene insertion G51D, Silke Nuber
MGI accession ID: MGI:7643545
Generation method: Transgenic
Attributes: Inserted expressed sequence; Humanized sequence
Synonyms: Thy1-G51D; Tg(Thy1-SNCA*)1Dett
Marker symbol: Tg(Thy1-SNCA*)G51DNuber
Marker name: transgene insertion G51D, Silke Nuber
Marker synonyms: Tg(Thy1-SNCA*)1Dett
Chromosome: UN
Strain of origin: C57BL/6J
Molecular note: Full-length human SCNA cDNA was mutagenized to carry a G51D mutation (nucleotide change: GGT to GAT in exon 3) and placed under the control of the mouse Thy1 neuronal promoter.