B6.Cg-Gt(ROSA)26Sor^{tm1(LRRK2*R1441C)Djmo}/J

Stock number: 026293
Strain synonyms: ROSA26-LRRK2 transgenic mice
Research areas: Neurobiology Research

Description

These ROSA26-LRRK2 (R1441C) mice allow cre-inducible expression of the familial Parkinson's disease-associated R1441C missense mutant form of LRRK2, and may be useful for studying Parkinson's disease pathogenesis and neurodegeneration.

Detailed description

These mice carry a targeted mutation in which a floxed STOP cassette and mutant human LRRK2 (R1441C) sequence was inserted into the endogenous Gt(ROSA)26Sor locus. The R1441C mutation occurs in the 'Ras of complex proteins' (ROC) domain of the leucine-rich repeat kinase 2 protein, reducing GTPase activity. Homozygotes are viable and fertile.

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.

Of note, the ROSA26-LRRK2 (R1441C) strain is also available on the original STOCK genetic background(Stock No. 022793).

Development

A targeting vector containing a SV40 splice acceptor, a loxP-flanked STOP cassette (PGK-neo and triple SV40 transcriptional termination sequence), a full-length human leucine-rich repeat kinase 2 cDNA bearing a familial Parkinson's disease-linked missense mutation R1441C, and a bovine polyadenylation signal was utilized in the generation of this strain. The construct was inserted into the Gt(ROSA)26Sor locus via electroporation into 129/SvJ-derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts and chimeric mice were bred with C57BL/6J mice to generate the mutant colony. The donating investigator reported that mice were backcrossed to C57BL/6J for at least 5 generations prior to arrival at The Jackson Laboratory. Upon arrival, mutant mice were bred with C57BL/6J inbred mice (Stock No. 000664) for at least 5 generations.

Allele

Symbol: Gt(ROSA)26Sor^{tm1(LRRK2*R1441C)Djmo}
Name: targeted mutation 1, Darren Moore
MGI accession ID: MGI:5527542
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); Inserted expressed sequence; Humanized sequence
Marker symbol: Gt(ROSA)26Sor
Marker name: gene trap ROSA 26, Philippe Soriano
Chromosome: 6
Strain of origin: 129
Expressed genes: LRRK2,leucine rich repeat kinase 2,human
Molecular note: The targeting vector contains a SV40 splice acceptor, a loxP-flanked STOP cassette (PGK-neo and triple SV40 transcriptional termination sequence), a full-length human leucine-rich repeat kinase 2 cDNA bearing a familial Parkinson's disease-linked missense mutation R1441C, and a bovine polyadenylation signal.