B6.129P2-Sncg^tm1Vlb/J

Stock number: 008843
Research areas: Neurobiology Research

Description

These mice harbor a null mutation of the γ-synuclein gene (Sncg) and may be useful in studying synuclein function in neurodegenerative diseases, such as Parkinson's disease.

Detailed description

Mice homozygous for this γ-synuclein mutant allele are viable and fertile with no obvious abnormalities in development, behavior, or gross morphology of the nervous system. No RNA or protein expression from the targeted gene is observed. Slight upregulation of β-synuclein is reported in the midbrain of homozygous mice. Homozygous mice are also resistant to the inflammatory/apoptotic Parkinson's disease-like pathology that results following MPTP neurotoxin administration (the active form of which (MPP+) gains entry into dopaminergic cells via the dopamine transporter (DAT)). These γ-synuclein mutant mice may be useful in studying synuclein function in neurodegenerative diseases, such as Parkinson's disease.

Development

A targeting vector was designed to replace exons 1-3 of the targeted gene with a PGK-neo cassette. The construct was electroporated into 129P2/OlaHsd derived E14TG2a embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts and the resulting chimeric animals were bred with C57BL/6J inbred mice. Next, mutant mice were backcrossed to C57BL/6J for at least 12 generations prior to arrival at The Jackson Laboratory. Upon arrival, mice were bred with C57BL/6J inbred mice (Stock No. 000664) to establish the colony.

Allele

Symbol: Sncg^tm1Vlb
Name: targeted mutation 1, Vladimir L Buchman
MGI accession ID: MGI:2683142
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Sncg
Marker name: synuclein, gamma
Chromosome: 14
Strain of origin: 129P2/OlaHsd
Molecular note: Exons 1 through 3 were replaced with a neomycin selection cassette inserted by homologous recombination. Transcript was undetected in homozygous mutant mice by Northern blot analysis of RNA obtained from various tissues. Western blot analysis of total spinal cord protein indicated an absence of protein in homozygous mutant mice.