STOCK Tg(tetO-SNCA*A53T)E2Cai/J

Stock number: 012442
Research areas: Neurobiology Research, Research Tools

Description

These transgenic mice carry a humanized synuclein (alpha-syn) mutant (SNCA*A53T) gene regulated by a tetracycline operator (tetO). When mated to a mutant strain expressing tTA, expression of SNCA*A53T protein may be regulated with the tetracycline analog doxycycline in the double mutant offspring.

Detailed description

Mice hemizygous for the human synuclein (alpha-syn) mutant transgene, (SNCA*A53T) are viable and fertile. Expression of SNCA*A53T is regulated by the tetracycline operator (tetO); also called tetracycline-responsive element (TRE, TetRE) or tet-operator). When mated to a mutant strain expressing tetracycline-controlled transactivator protein (tTA), expression of SNCA*A53T protein may be regulated with tetracycline or its analog doxycycline (dox) in the double mutant offspring. Mutations in alpha-syn greatly accelerate the 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*A53T 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.

Development

A transgene was generated encoding a human SNCA*A53T mutant 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 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 performed by The Jackson Laboratory revealed 10 of 32 markers (on six different chromosomes) that were not C57BL/6J allele-type. These data suggest C57BL/6N, FVB, and/or other genetic contamination prior to arrival at The Jackson Laboratory.

Allele

Symbol: Tg(tetO-SNCA*A53T)E2Cai
Name: transgene insertion E2, Huaibin Cai
MGI accession ID: MGI:4420801
Generation method: Transgenic
Attributes: Inducible; Inserted expressed sequence; Humanized sequence
Marker symbol: Tg(tetO-SNCA*A53T)E2Cai
Marker name: transgene insertion E2, Huaibin Cai
Chromosome: UN
Strain of origin: C57BL/6J
Expressed genes: SNCA,synuclein alpha,human
Molecular note: A transgenic vector was generated encoding a human SNCA*A53T mutant gene under the control of a tetO promoter. The construct was microinjected into C57BL/6J fertilized oocytes, and founder mice were bred to C57BL/6J mice to establish the E2 line.