B6(SJL)-Lrrk2^tm2.1Mjff/J

Stock number: 021829
Product name: Lrrk2^T1348N
Research areas: Neurobiology Research

Description

This strain carries the T1348N point mutation in the Parkinson's disease-related Lrrk2 gene. The LRRK2 T1348N mutant protein has been shown to inhibit GTPase activity.

Detailed description

This strain carries the T1348N point mutation in the Parkinson's disease-related Lrrk2 gene which corresponds to the human LRRK2 T1348N point mutation in the guanine nucleotide binding site. The "GTPase dead" mutant protein has been shown to inhibit GTPase activity. This strain has not yet been characterized (September 2015).

Development

A targeting vector was designed to introduce a threonine to asparagine (T1348N) substitution at codon 1348 in exon 29 of the endogeneous locus. In addition, an FRT-flanked neomycin resistance (neo) cassette was introduced approximately 200 bp downstream of exon 29. The construct was electroporated into C57BL/6N-derived JM8 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and chimeric mice were bred to C57BL/6NJ inbred mice (Stock No. 005304) to create heterozygous mice. Heterozygous mice were then bred to B6.Cg-Tg(ACTFLPe)9205Dym/J (Stock No. 005703) to remove the neo cassette and leave a silent FRT site. The resulting animals were crossed to C57BL/6NJ inbred mice (Stock No. 005304) for one generation.

Allele

Symbol: Lrrk2^tm2.1Mjff
Name: targeted mutation 2.1, The Michael J Fox Foundation
MGI accession ID: MGI:5466852
Generation method: Targeted
Attributes: Humanized sequence
Marker symbol: Lrrk2
Marker name: leucine-rich repeat kinase 2
Chromosome: 15
Strain of origin: C57BL/6N
Molecular note: A targeting vector was designed to introduce a threonine to asparagine (T1348N) substitution at codon 1348 in exon 29 of the endogeneous locus. In addition, an FRT-flanked neomycin resistance (neo) cassette was introduced approximately 200 bp downstream of exon 29. Flp-mediated recombination removed the FRT-flanked neo cassette.