STOCK Tg(teto-LRRK2)C7874Cai/J

Stock number: 012449
Product name: tetO-LRRK2
Strain synonyms: TRE-LRRK2
Research areas: Neurobiology Research, Research Tools

Description

These hemizygous transgenic mice carry a human leucine-rich repeat kinase 2 gene, LRRK2, regulated by a tetracycline operator (tetO). When mated to a mutant strain expressing tetracycline-controlled transactivator protein (tTA), expression of LRRK2 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.

Detailed description

Mice hemizygous for the human leucine-rich repeat kinase 2 transgene, (LRRK2), are viable and fertile. Expression of LRRK2 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 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. These mice may be useful for studying Parkinson's disease pathogenesis and neurodegeneration.

Development

A transgenic vector was generated encoding the C-terminal hemagglutinin (HA)-tagged human LRRK2 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 (see 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 performed by The Jackson Laboratory revealed 6 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-LRRK2)C7874Cai
Name: transgene insertion C7874, Huaibin Cai
MGI accession ID: MGI:4420758
Generation method: Transgenic
Attributes: Inducible; Inserted expressed sequence; Humanized sequence
Marker symbol: Tg(tetO-LRRK2)C7874Cai
Marker name: transgene insertion C7874, Huaibin Cai
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 gene under the control of a tetO promoter. The construct was microinjected into C57BL/6J fertilized oocytes, and 5 independent lines were generated including line C7874. Founder mice were bred to C57BL/6J mice to establish this colony.