FVB.Cg-Pde6b⁺ Lrrk1^tm1.1Mjff Tyr^c-ch/J

Stock number: 022880
Research areas: Dermatology Research, Developmental Biology Research, Mouse/Human Gene Homologs, Neurobiology Research, Sensorineural Research

Description

These Lrrk1 knock-out mice may be useful for studying the role of Lrrk1 in the progression of Parkinson's Disease.

Detailed description

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. On the C57BL/6 background, homozygous pups do not survive until weaning. To date, homozygotes have not been generated on the FVB background. Information will be added as it becomes available. These mice may be useful for studying the role of Lrrk1 in the progression of Parkinson's Disease.

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.

Development

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/6 genetic background prior to sending to The Jackson Laboratory. At The Jackson Laboratory, the allele was introgressed into FVB.129P2-Pde6b⁺ Tyr^c-ch/AntJ (Stock No. 004828) for at least five generations. These mice are homozygous for the 129P2/OlaHsd wildtype Pde6b allele and do not suffer from blindness due to retinal degeneration. They also are pigmented as a result of the homozygosity of the Tyr^c-ch (chinchilla) allele.

Allele

Symbol: Pde6b⁺
Name: wild type
MGI accession ID: MGI:2430003
Generation method: Not Applicable
Marker symbol: Pde6b
Marker name: phosphodiesterase 6B, cGMP, rod receptor, beta polypeptide
Chromosome: 5
Strain of origin: Not Applicable
Expressed genes: Pde6b,phosphodiesterase 6B, cGMP, rod receptor, beta polypeptide,mouse, laboratory
Site of expression: Retina.

Allele

Symbol: Tyr^c-ch
Name: chinchilla
MGI accession ID: MGI:1855977
Generation method: Spontaneous
Marker symbol: Tyr
Marker name: tyrosinase
Chromosome: 7
Strain of origin: fancier's stock
Molecular note: The mutation in the chinchilla allele was found to be a G-to-A point mutation that results in an amino acid change at position 482 or 464 from alanine to threonine (p.A482T for pre-protein, p.A464T for mature protein).

Allele

Symbol: Lrrk1^tm1.1Mjff
Name: targeted mutation 1.1, The Michael J Fox Foundation
MGI accession ID: MGI:4940302
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Lrrk1
Marker name: leucine-rich repeat kinase 1
Chromosome: 7
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.