These hemizygous transgenic mice carry a humanized leucine-rich repeat kinase 2 mutant gene, LRRK2*G2019S, regulated by a tetracycline operator (tetO). When mated to a mutant strain expressing tetracycline-controlled transactivator protein (tTA), expression of LRRK2*G2019S 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 dominant toxic effects of mutant LRRK2*G2019S expression.
Huaibin Cai, National Institutes of Health / National Institute on Aging (NIH/NIA)
Genetic Background | Generation |
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Allele Type |
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Transgenic (Inducible, Inserted expressed sequence, Humanized sequence) |
Mice hemizygous for the human leucine-rich repeat kinase 2 mutant transgene, (LRRK2*G2019S), are viable and fertile. Expression of LRRK2*G2019S is regulated by a 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 LRRK2*G2019S protein may be regulated with tetracycline or its analog doxycycline (dox) in the double mutant offspring. LRRK2 protein, also known as Dardarin, contains multiple functional domains and may function as both an active GTPase and kinase. LRRK2 may regulate alpha-synuclein-mediated neuropathology through modulating the intracellular trafficking and accumulation of SNCA protein. The amino acid mutation in the kinase domain of LRRK2 may decrease proteasomal degradation of LRRK2. These mice may be useful for studying Parkinson's disease pathogenesis and neurodegeneration elicited by the dominant toxic effects of mutant LRRK2*G2019S expression.
When bred to a strain expressing tTA in forebrain neurons (see Stock No. 007004 for example), this mutant mouse strain may be useful in studies of neuronal morphegenesis.
A transgenic vector was generated encoding the C-terminal hemagglutinin (HA)-tagged human LRRK2*G2019S mutant gene under control of a tetO promoter. The donating investigator reported that the construct was microinjected into C57BL/6J fertilized oocytes, and founder mice were bred to C57BL/6J mice to establish a colony (see SNP note below). 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. Five markers, on Ch 1, 2, 4, 5, and 11, were found to be segregating, suggesting mice sent to The Jackson Laboratory Repository were on a mixed genetic background.
Expressed Gene | LRRK2, leucine rich repeat kinase 2, human |
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Site of Expression |
Allele Name | transgene insertion E3, Huaibin Cai |
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Allele Type | Transgenic (Inducible, Inserted expressed sequence, Humanized sequence) |
Allele Synonym(s) | G2019S; LRRK2 G2019S; tetO-LRRK2 G2019S |
Gene Symbol and Name | Tg(tetO-LRRK2*G2019S)E3Cai, transgene insertion E3, Huaibin Cai |
Gene Synonym(s) | |
Promoter | tetO, tet operator, |
Expressed Gene | LRRK2, leucine rich repeat kinase 2, human |
Strain of Origin | C57BL/6J |
Chromosome | UN |
Molecular Note | A transgenic vector was generated encoding the C-terminal hemagglutinin (HA)-tagged human LRRK2*G2019S mutant gene under control of a tetO promoter. The construct was microinjected into C57BL/6J fertilized oocytes, and three independent lines were generated. Founder mice were bred to C57BL/6J mice to establish the E3 line. |
Mutations Made By | Huaibin Cai, National Institutes of Health / National Institute on Aging (NIH/NIA) |
When maintained as a live colony, homozygous mice may be bred together or transgene carrier mice may be bred to wild type siblings.
When using the STOCK Tg(tetO-LRRK2*G2019S)E3Cai/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #012441 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
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Hemizygous or Non carrier for Tg(tetO-LRRK2*G2019S)E3Cai |
Frozen Mouse Embryo | STOCK Tg(tetO-LRRK2*G2019S)E3Cai/J | $2595.00 |
Frozen Mouse Embryo | STOCK Tg(tetO-LRRK2*G2019S)E3Cai/J | $2595.00 |
Frozen Mouse Embryo | STOCK Tg(tetO-LRRK2*G2019S)E3Cai/J | $3373.50 |
Frozen Mouse Embryo | STOCK Tg(tetO-LRRK2*G2019S)E3Cai/J | $3373.50 |
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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.
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