C57BL/6-Lrrk2^tm1Mjfa/J

Stock number: 012444
Research areas: Neurobiology Research, Research Tools

Description

This LRRK2 knock-out targeted mutation strain exhibits enhanced neuritic outgrowth and may be useful in studies of dendritic neuronal arborization and Parkinson's disease.

Detailed description

Mice that are homozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. Exon 41, which encodes the kinase domain, is deleted. Homozygotes exhibit increased mean process length and branching in primary neurons from the hippocampus and midbrain. Heterozygotes and wildtype controls exhibit similar neuritic outgrowth.

Development

This strain was generated at the Mayo Clinic, Jacksonville, FL. A targeting vector containing a PGK-neo cassette was used to insert loxP sites flanking exon 41 and the selection cassette. The construct was electroporated into C57BL/6 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts. The resulting chimeric animals were crossed to mice expressing Cre recombinase (on the C57BL/6 background) to remove exon 41 and the PGK-neo cassette. Heterozygotes were crossed to generate homozygotes. Upon arrival at The Jackson Laboratory, the mice were crossed with C57BL/6J to establish the colony (see SNP note below).

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. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, 2 of 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a mixed C57BL/6J ; C57BL/6N genetic background.

Allele

Symbol: Lrrk2^tm1Mjfa
Name: targeted mutation 1, Matthew Farrer
MGI accession ID: MGI:5008465
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Lrrk2
Marker name: leucine-rich repeat kinase 2
Chromosome: 15
Strain of origin: B6.Cg-Thy1^a
Molecular note: A targeting vector containing a PGK-neo cassette was used to insert loxP sites flanking exon 41 and the selection cassette. Cre-mediated recombination removed exon 41 and the FRT-flanked neo cassette.