These Lrrk1 knock-out mice may be useful for studying the role of Lrrk1 in the progression of Parkinson's Disease.
Kuldip Dave, The Michael J. Fox Foundation
These mice lack exons 24-29 of the leucine-rich repeat kinase 1 (Lrrk1) gene, abolishing gene function. LRRK1 is a gene homolog of Lrrk2, mutations of which have been associated with Parkinson's disease. LRRK1 regulates endosomal trafficking of the EGF receptor. These mice may be useful for studying the role of Lrrk1 in the progression of Parkinson's Disease.
Preliminary evidence from colonies at The Jackson Laboratory indicates that homozygous mice do not survive to wean age at the expected frequency.
A targeting vector was designed to replace exons 24-29 of the leucine-rich repeat kinase 1 (Lrrk1) gene with a loxP-flanked neomycin resistance (neo) cassette. The construct was electroporated into C57BL/6Tac-derived B6-3 embryonic stem (ES) cells. Correctly targeted ES cells were transiently transfected with a Cre recombinase expression plasmid to delete the neo cassette. Correctly targeted ES cells were injected into blastocysts and chimeric mice were bred to C57BL/6NTac mice. The donating investigator reports that mutant mice were maintained on a C57BL/6NTac genetic background (see SNP note below) prior to sending to The Jackson Laboratory. Upon arrival, heterozygous sperm was frozen. To generate the live colony, an aliquot of the frozen sperm was used to fertilize oocytes from C57BL/6NJ inbred females (Stock No. 005304).
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, all 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 C57BL/6J genetic background.
|Allele Name||targeted mutation 1.1, The Michael J Fox Foundation|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Lrrk1, leucine-rich repeat kinase 1|
|Strain of Origin||C57BL/6NTac|
|Molecular Note||A targeting vector replaced exons 24-29 of the leucine-rich repeat kinase 1 (Lrrk1) gene with a loxP-flanked neomycin resistance (neo) cassette. Cre-mediated recombination removed the neo cassette.|
|Mutations Made By|| |
Yingbin Ouyang, Taconic
When maintaining a live colony, heterozygous mice may be bred to wildtype mice from the colony.
When using the LRRK1 KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #016120 in your Materials and Methods section.