B6;D2-Tg(Mbp-SNCA)1Ema/RoriJ

Stock number: 038895
Product name: MBP hα-syn Line 1
Research areas: Neurobiology Research

Description

MBP hα-syn Line 1 transgenic mice express wildtype human α-synuclein cDNA driven by the mouse Mbp promoter. These mice may be useful in studying human neuronal α-synucleinopathies, such as multiple systems atrophy (MSA).

Note that the donating laboratory has made multiple human SNCA transgenic lines available, including the higher-expressing MBP hα-syn Line 29 mouse model (Stock No. 038896). Other SNCA lines made available by this donating investigator include SNCA*E57K(16) (Stock No. 038773), PDGFβ-hαsyn-eGFP (Stock No. 038774), D Line PDGFβ-hαsyn (Stock No. 038775) and Line 61 mThy1 hα-syn Tg (Stock No. 038796).

Detailed description

α-Synuclein is a neuronal protein (coded by Snca) which plays a role in synaptic plasticity and neurotransmitter release. Mutations of Snca have been implicated in a group of neurodegenerative diseases that result from an accumulation of α-synuclein in neurons or, in some cases, glial cells. These disorders include Parkinson's disease, dementia with Lewy bodies, the Lewy body variant of Alzheimer's disease (AD), multiple system atrophy, and neurodegeneration with brain iron accumulation.

MBP hα-syn Line 1 transgenic mice express full length human wildtype α-synuclein cDNA driven by the murine myelin basic protein (Mbp) promoter, resulting in progressive α-synuclein aggregation in oligodendrocytes as well as in cortical and subcortical brain regions.

Hemizygous MBP hα-syn Line 1 transgenic mice are viable and fertile, but do demonstrate a mild tremor phenotype. Homozygous transgenic mice have not been evaluated by the donating laboratory (October 2023). Compared to the high-expressing MBP hα-syn Line 29 transgenic mice (Stock No. 038896), which demonstrate a shortened lifespan of 6 months, the hemizygous MBP hα-syn Line 1 mice have a lifespan of at least 18 months. These mice may be used when studying the pathogenesis of synucleinopathies, specifically pathologies associated with multiple system atrophy (MSA).

Note that the donating laboratory has made multiple human SNCA transgenic lines available, including the higher-expressing MBP hα-syn Line 29 mouse model (Stock No. 038896). Other SNCA lines made available by this donating investigator include SNCA*E57K(16) (Stock No. 038773), PDGFβ-hαsyn-eGFP (Stock No. 038774), D Line PDGFβ-hαsyn (Stock No. 038775) and Line 61 mThy1 hα-syn Tg (Stock No. 038796).

Development

The MBP hα-syn Line 1 transgene was generated using human synuclein, alpha (SNCA) cDNA driven by the mouse myelin basic protein (Mbp) promoter. The construct contains the Mbp promoter sequence, an SV40 splice site, 423 bp of human cDNA encoding full length wild-type SNCA (nucleotides 53-475; GenBank accession number L08850) and SV40 polyadenylation sequences. The hα-syn cDNA fragments were ligated with the 5' upstream region of the MBP cassette; the splice and the polyadenylation signals were supplied by portions of the PLP gene (exon 6, intron 6, exon 7). Purified linearized DNA was microinjected into the pronuclei of fertilized (C57BL/6 x DBA/2)F1 mouse oocytes. Four founder lines were generated (1, 2, 29 and 31) of which line 29 (Stock No. 038896) was the highest-expressing line followed by line 1. The donating laboratory has indicated that the integration site and copy number are not known. These transgenic mice were maintained on a mixed B6;D2 background. Upon arrival, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize B6D2F1 (Stock No. 100006) oocytes.

Allele

Symbol: Tg(Mbp-SNCA)1Ema
Name: transgene insertion 1, Eliezer Masliah
MGI accession ID: MGI:5634092
Generation method: Transgenic
Attributes: Inserted expressed sequence; Humanized sequence
Synonyms: MBP halpha-syn tg
Marker symbol: Tg(Mbp-SNCA)1Ema
Marker name: transgene insertion 1, Eliezer Masliah
Marker synonyms: MBP halpha-syn tg
Chromosome: UN
Strain of origin: (C57BL/6 x DBA/2)F1
Molecular note: The murine Mbp promoter drives the expression of human alpha-synuclein cDNA (nucleotides 53-475). Line 1 is a lower expressor than line 29. Highest mRNA expression is seen in the corpus callosum, followed by white matter tracts in the brainstem, spinal cord, basal ganglia, and cerebellum and lowest levels in the hippocampus, neocortex, and cortical layers in the cerebellum. Immunohistochemical analysis indicates protein expression in glial but not neuroal cells of the neocortex, basal ganglia, corpus callosum and cerebellum. Four lines were generated; 1, 2, 29, and 31.