STOCK Tg(tetO-LRRK2*G2019S)E3Cai/J

Stock number: 012441
Research areas: Neurobiology Research, Research Tools

Description

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.

Detailed description

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.

Development

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.

Allele

Symbol: Tg(tetO-LRRK2*G2019S)E3Cai
Name: transgene insertion E3, Huaibin Cai
MGI accession ID: MGI:4420755
Generation method: Transgenic
Attributes: Inducible; Inserted expressed sequence; Humanized sequence
Synonyms: G2019S; LRRK2 G2019S; tetO-LRRK2 G2019S
Marker symbol: Tg(tetO-LRRK2*G2019S)E3Cai
Marker name: transgene insertion E3, Huaibin Cai
Marker synonyms: G2019S; LRRK2 G2019S; tetO-LRRK2 G2019S
Chromosome: UN
Strain of origin: C57BL/6J
Expressed genes: LRRK2,leucine rich repeat kinase 2,human
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.