B6;D2-Tg(tetO-SNCA)1Cai/J

Stock number: 012450
Research areas: Neurobiology Research, Research Tools

Description

These hemizygous transgenic mice carry a human synuclein (alpha-syn) gene, SNCA, regulated by a tetracycline operator (tetO). When mated to a mutant strain expressing tetracycline-controlled transactivator protein (tTA), expression of SNCA protein may be regulated with the tetracycline analog doxycycline (dox) in the double mutant offspring. These mice may be useful for studying the Parkinson's disease pathogenesis and neurodegeneration elicited by the toxic effects of aggregation and somatic accumulation of SNCA.

Detailed description

Mice hemizygous for the human synuclein (alpha-syn) transgene, (SNCA) are viable and fertile. Expression of the transgene is regulated by the tetracycline operator (tetO); also called tetracycline-responsive element (TRE, TetRE) or tet-operator). When mated to a strain expressing tetracycline-controlled transactivator protein (tTA), expression of the SNCA protein may be regulated with tetracycline or its analog doxycycline (dox) in the double mutant offspring. The formation of alpha-syn aggregates is a key step in the pathogenesis of Parkinson's disease. These aggregates cause formation of fibrillar aggregates causing various forms of cytotoxicity, including impairment of proteasomal and lysosomal activities, disruption of ER-Golgi traffic and microtubule-based transport, and dysfunction of mitochondria. SNCA mice develop age-dependent, progressive neurodegeneration. These mice may be useful for studying the Parkinson's disease pathogenesis and neurodegeneration elicited by the toxic effects of aggregation and somatic accumulation of SNCA.

For example, when bred to a strain expressing rtTA or tTA in forebrain neurons (see Stock No. 007004 for example), this mutant mouse strain may be useful in studies of neurodegeneration.

Development

A transgenic vector was generated encoding the C-terminal hemagglutinin (HA)-tagged human SNCA gene under control of a tetO promoter. The construct was microinjected into C57BL/6J fertilized oocytes, and founder mice were bred to C57BL/6J mice (see SNP note below) to establish a colony. Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony.

A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 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 rederived living colony at The Jackson Laboratory Repository. 6 markers were found to be segregating for DBA/J from an unknown source.

Allele

Symbol: Tg(tetO-SNCA)1Cai
Name: transgene insertion 1, Huaibin Cai
MGI accession ID: MGI:4420977
Generation method: Transgenic
Attributes: Inducible; Inserted expressed sequence; Humanized sequence
Marker symbol: Tg(tetO-SNCA)1Cai
Marker name: transgene insertion 1, Huaibin Cai
Chromosome: UN
Strain of origin: C57BL/6
Expressed genes: SNCA,synuclein alpha,human
Molecular note: A transgenic vector was generated encoding the human SNCA gene under the control of a tetO promoter. The construct was microinjected into fertilized oocytes, and a line of mice was established.