B6;D2-Tg(Thy1-SNCA*E57K)16Ema/RoriJ

Stock number: 038773
Product name: SNCA*E57K(16)
Research areas: Neurobiology Research

Description

SNCA*E57K(16) transgenic mice express human α-synuclein that contains an E57K amino acid substitution driven by the mouse thymus cell antigen 1, theta (Thy1) promoter. These mice may be useful in studying human neuronal α-synucleinopathies, such as familial Parkinson's disease.

Of note, the donating investigator has also made their wildtype mThy-1 hα-synuclein transgenic mouse line 61 available as 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. SNCA*E57K(16) transgenic mice express human α-synuclein that contains an E57K amino acid substitution driven by the mouse thymus cell antigen 1, theta (Thy1) promoter. This mutation results in expression of an altered α-synuclein that preferentially form oligomers, as opposed to fibrils. This oligomer-prone species of α-synuclein has been found to increase degeneration of dopaminergic neurons and synaptic damage.

Hemizygous SNCA*E57K(16) transgenic mice are viable and fertile; homozygous SNCA*E57K(16) mice have not been evaluated by the donating laboratory (September 2023). The donating laboratory noted that these SNCA*E57K(16) transgenic mice displayed similar levels of synaptic degeneration and neuronal loss in the hippocampus when compared to transgenic mice harboring the full-length wildtype human α-synuclein (Stock No. 038796); however, they differed in that the oligomer-prone mice displayed more severe synaptic pathology, behavioral differences and neuronal loss in the frontal cortex. These mice may be used when studying human neuronal α-synucleinopathies, such as Parkinson's disease.

Development

The SNCA*E57K(16) transgene was generated using human synuclein, alpha (SNCA) cDNA (GenBank# NM_000345), containing the E57K mutation, under the control of the mouse Thy1 gene promoter. The SNCA E57K cDNA fragment was ligated into pCRII (Invitrogen), sequenced for accuracy, inserted into the mThy-1 expression cassette between exons 2 and 4, and purified. The purified linearized DNA was microinjected into the pronuclei of fertilized (C57BL/6 x DBA/2)F1 mouse oocytes. Three founder lines were established, founder line 16 was determined to have the highest expression. The donating laboratory has indicated that the integration site and copy number are not known. These transgenic mice were then 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(Thy1-SNCA*E57K)16Ema
Name: transgene insertion 16, Eliezer Masliah
MGI accession ID: MGI:5806788
Generation method: Transgenic
Attributes: Inserted expressed sequence; Humanized sequence
Synonyms: alpha-syn E57K tg; mThy1-alpha-syn E57K tg
Marker symbol: Tg(Thy1-SNCA*E57K)16Ema
Marker name: transgene insertion 16, Eliezer Masliah
Marker synonyms: alpha-syn E57K tg; mThy1-alpha-syn E57K tg
Chromosome: UN
Strain of origin: (C57BL/6 x DBA/2)F1
Molecular note: The human alpha-synuclein bearing the oligomer-prone E57K mutation is under the control of neuronal mouse Thy1 promoter. Three lines were generated. Lines 9 and 16 are high expressers, and line 54 is a lower expressing line. Size exclusion chromatography confirmed the formation of oligomeric alpha-synuclein.