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
Genetic Background | Generation |
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Allele Type | Gene Symbol | Gene Name |
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Targeted (Null/Knockout) | Lrrk2 | leucine-rich repeat kinase 2 |
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 |
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Allele Type | Targeted (Null/Knockout) |
Allele Synonym(s) | |
Gene Symbol and Name | Lrrk2, leucine-rich repeat kinase 2 |
Gene Synonym(s) | |
Strain of Origin | B6.Cg-Thy1a |
Chromosome | 15 |
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.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Heterozygous for Lrrk2<tm1Mjfa> |
Frozen Mouse Embryo | C57BL/6-Lrrk2<tm1Mjfa>/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | C57BL/6-Lrrk2<tm1Mjfa>/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | C57BL/6-Lrrk2<tm1Mjfa>/J Frozen Embryo | $3373.50 |
Frozen Mouse Embryo | C57BL/6-Lrrk2<tm1Mjfa>/J Frozen Embryo | $3373.50 |
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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.
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