B6;C3-Tg(tetO-AIMP2)630Tmd/J

Stock number: 023598
Research areas: Cell Biology Research, Neurobiology Research, Research Tools

Description

These tetO-AIMP2 mice may be useful for studying the Parkinson's disease pathogenesis and neurodegeneration elicited by the toxic effects of aggregation and somatic accumulation of AIMP2.

Detailed description

Mice hemizygous for the human aminoacyl tRNA synthetase complex-interacting multifunctional protein 2 (AIMP2) transgene 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). AIMP2 is a substrate of PARKIN (PARK2), an E3 ligase expressed in the brain that ubiquitinates damaged and excess proteins, marking them for degradation and clearance by proteasomes. Mutations of PARK have been implicated in the onset of Parkinson's disease, allowing pathogenic substrates, such as AIMP2, to accumulate. The buildup of these proteins disrupts normal cell activities, and impairs nerve cells, including dopamine-producing nerve cells. When mated to a strain expressing tetracycline-controlled transactivator protein (tTA), expression of the AIMP2 protein may be regulated with tetracycline or its analog doxycycline (dox) in the double mutant offspring.

For example, when mice from this founder line (630) are bred to B6.Cg-Tg(Camk2a-tTA)1Mmay/DboJ mice (Stock No. 007004) expressing tTA in forebrain neurons, double mutant offspring overexpress AIMP2 14-fold in neurons of the cortex and 4-fold in neurons of the ventral midbrain after. These mice exhibit progressive loss of 28% of their dopaminergic neurons in the ventral tegmental area by 20 months of age. They also exhibited progressive loss of neurons in the substantia nigra zona compacta, reaching 53% by 20 months of age. Mice from founder line 630 have higher AIMP2 expression in neurons of the cortex than mice from founder line 634 (Stock No. 023642).

Development

A transgenic vector was generated encoding the C-terminal FLAG-tagged human aminoacyl tRNA synthetase complex-interacting multifunctional protein 2 (AIMP2) gene under control of a tetO promoter. The construct was microinjected into B6C3F2 fertilized oocytes, and mice from founder line 630 were bred to C57BL/6 mice to establish a colony. Resulting offspring were bred to C57BL/6NCrl mice for at least 2 generations. Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6NJ inbred mice (Stock No. 005304) for at least one generation.

Allele

Symbol: Tg(tetO-AIMP2)630Tmd
Name: transgene insertion 630, Ted M Dawson
MGI accession ID: MGI:5506893
Generation method: Transgenic
Attributes: Inducible; Inserted expressed sequence; Humanized sequence
Marker symbol: Tg(tetO-AIMP2)630Tmd
Marker name: transgene insertion 630, Ted M Dawson
Chromosome: UN
Strain of origin: B6C3F2
Expressed genes: AIMP2,aminoacyl tRNA synthetase complex interacting multifunctional protein 2,human
Molecular note: The C-terminal FLAG-tagged human aminoacyl tRNA synthetase complex-interacting multifunctional protein 2 (AIMP2) gene was placed under control of a tetO promoter.