C57BL/6-Dnajc6^em1Mcook/J

Stock number: 034516
Product name: DNAJC6 R857G
Research areas: Neurobiology Research

Description

DNAJC6 R857G knock-in mice carry an R857G (arginine to glycine) substitution in the Dnajc6 (DnaJ heat shock protein family (Hsp40) member C6) gene. Homozygous adult mice develop abnormal motor phenotypes. This strain may be useful for studying juvenile Parkinsonism.

Detailed description

The Dnajc6 (DnaJ heat shock protein family (Hsp40) member C6 or auxilin) gene encodes a co-chaperone involved in the uncoating of clathrin coated vesicles (CCV) expressed in neurons in the central nervous system. Auxilin functions as the major neuronal uncoating protein required for regulation and trafficking of CCVs derived from the trans-Golgi network. Mutations in Dnajc6 are associated with juvenile Parkinson's disease. The coding mutation R927G (mouse R857G) was identified by the International Parkinsonism Genetics Network. DNAJC6 R857G knock-in mice are viable and fertile. Older mice (over 6 months of age) homozygous for the mutation develop motor phenotypes (bradykinesia, gait problems, decreased agility) as well as seizures in a subset of mice. This strain may be useful for studying juvenile Parkinsonism.

Development

CRISPR/cas9 endonuclease-mediated genome editing was used to create an amino acid substitution at position 857 altering arginine to glycine (R857G; AGG to GGC) in the Hspa8 (formerly Hsc70) binding domain of the Dnajc6 (DnaJ heat shock protein family (Hsp40) member C6) gene. The mutation is orthologous to the pathogenic human R927G allele associated with juvenile Parkinsonism. Single guide RNA and Cas9 endonuclease were introduced into C57BL/6-derived fertilized eggs by pronuclear injection. Embryos were transferred to pseudopregnant females, and correctly targeted pups were bred to C57BL/6J mice for germline transmission. The mutation was confirmed by sequencing. The colony was maintained on the C57BL/6J background. Upon arrival, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes.

Allele

Symbol: Dnajc6^em1Mcook
Name: endonuclease-mediated mutation 1, Mark Cookson
MGI accession ID: MGI:6382419
Generation method: Endonuclease-mediated
Attributes: Humanized sequence
Synonyms: R857G Auxilin
Marker symbol: Dnajc6
Marker name: DnaJ heat shock protein family (Hsp40) member C6
Marker synonyms: 2810027M23Rik; auxilin; DJC6; mKIAA0473; PARK19
Chromosome: 4
Strain of origin: C57BL/6
Molecular note: CRISPR/cas9 endonuclease-mediated genome editing is used to create an amino acid substitution at position 857 altering arginine to glycine (R857G; AGG to GGC) in the Hspa8 binding domain of the gene. The mutation is orthologous to the pathogenic human R927G allele associated with juvenile Parkinsonism.