B6.Cg-Tg(Lrrk2)6Yue/J

Stock number: 012466
Research areas: Developmental Biology Research, Neurobiology Research

Description

These FLAG-Lrrk2-WT mice express a wild-type mouse leucine-rich repeat kinase 2 (Lrrk2) gene directed by its endogenous promoter/enhancer regions on a BAC transgene. These mice may be useful for studying normal function of LRRK2 function and the pathogenesis of Parkinson's disease.

Detailed description

Mice hemizygous for the BAC FLAG-Lrrk2-Wt transgene are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. These mice express a wild-type mouse leucine-rich repeat kinase 2 (Lrrk2) gene directed by its endogenous promoter/enhancer regions on the BAC transgene. These BAC FLAG-Lrrk2-Wt mice "overexpress" the wildtype mouse LRRK2 protein in cerebral cortex, striatum, substantia nigra, internal capsule, and hippocampus at an approximately 6-8 fold greater level than endogenous mouse Lrrk2. Contrary to the BAC FLAG-Lrrk2-G2019S Parkinson's disease mice, these mice have enhanced evoked dopamine release in the striatum and exhibit slightly increased motor activities compared to nontransgenic wild-type controls. These mice may be useful for studying normal function of LRRK2 function and the pathogenesis of Parkinson's disease.

Development

Bacterial artificial chromosome (BAC) library (CHORI) was used to obtain a 240 kb BAC (#RP23-312I9) containing the entire mouse Lrrk2 (leucine-rich repeat kinase 2) gene. This BAC, containing a FLAG-tag downstream from the start codon, was microinjected into fertilized B6C3 F1 oocytes. FLAG-Lrrk2-WT founder line 6 was established and then subsequently maintained by breeding transgenic mice with C57BL/6J inbred mice for at least 12 generations prior to arrival at The Jackson Laboratory. Upon arrival, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony.

Allele

Symbol: Tg(Lrrk2)6Yue
Name: transgene insertion 6, Zhenyu Yue
MGI accession ID: MGI:4437427
Generation method: Transgenic
Attributes: Inserted expressed sequence
Synonyms: FLAG-LRRK2-WT; LRRK2-WT^OE
Marker symbol: Tg(Lrrk2)6Yue
Marker name: transgene insertion 6, Zhenyu Yue
Marker synonyms: FLAG-LRRK2-WT
Chromosome: UN
Strain of origin: (C57BL/6 x C3H)F1
Expressed genes: Lrrk2,leucine-rich repeat kinase 2,mouse, laboratory
Molecular note: Bacterial artificial chromosome (BAC) library (CHORI) was used to obtain a 240 kb BAC (#RP23-312I9) containing the entire mouse Lrrk2 (leucine-rich repeat kinase 2) gene. This BAC contains a FLAG-tag downstream from the start codon. Founder line 6 was established with expression in cerebral cortex, striatum, substantia nigra, internal capsule, and hippocampus at an approximately 6-8 fold greater level than endogenous mouse Lrrk2.