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.
Dr. Matthew J Farrer, University of British Columbia
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.
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 Name||targeted mutation 1, Matthew Farrer|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Lrrk2, leucine-rich repeat kinase 2|
|Strain of Origin||B6.Cg-Thy1a|
|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.|
|Mutations Made By|| |
Dr. Matthew Farrer, University of British Columbia
When maintaining a live colony, these mice can be bred as homozygotes.
When using the C57BL/6-Lrrk2tm1Mjfa/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #012444 in your Materials and Methods section.