B6.Cg-Vps35^tm1.1Smsa/J

Stock number: 040711
Product name: VPS35 floxed
Research areas: Cell Biology Research, Neurobiology Research, Research Tools

Description

Vps35^flox mice carry loxP sites flanking exons 3-5 of the Vps35 gene. These mice may be useful when studying the role of VPS35 in endosomal protein trafficking in neurodegenerative diseases, such as Parkinson's disease (PD) and Alzheimer's disease (AD).

Detailed description

The Vps35 (VPS35 retromer complex component) gene codes for a component of the retromer complex, which is involved in retrograde transport from endosomes to the trans-Golgi network and protein homeostasis. Mutations in this gene have been implicated in neurodegenerative disorders, such as Parkinson's disease and Alzheimer's disease. These Vps35^flox mice possess loxP sites flanking exons 3-5 of the Vps35 gene.

Homozygous mice are viable and fertile with no overt phenotype. When bred to mice that express tissue-specific Cre recombinase, resulting offspring will have exons 3-5 deleted in the cre-expressing tissues, resulting in complete loss of VP3S35 protein. When these floxed mice are crossed to a Camk2α-Cre mouse line (Stock No. 005359), resulting Vps35^fl/fl; Camk2α-Cre knock-out (KO) progeny demonstrated complete loss of VPS35 protein in forebrain neurons as anticipated.

These Vps35^flox mice maybe useful when studying endosomal protein trafficking in neurodegenerative diseases.

Development

The Vps35^flox targeting vector was designed to insert loxP sites flanking exons 3-5 of the VPS35 retromer complex component (Vps35) gene. The targeting construct included an initial loxP site upstream of exon 3, followed by an FRT-flanked neomycin selection cassette and a second loxP site inserted downstream of exon 5. The construct was electroporated into (C57BL/6Jx129/Sv)F1-derived embryonic stem (ES) cells and correctly targeted ES cells were injected into recipient blastocysts. Chimeric mice were bred to a ROSA26-Flpe recombinase mouse line, on a C57BL/6 background, to excise the neomycin cassette. Resulting Vps35^flox mice, with neo cassette removed and floxed exons 3-5 intact, were further back-crossed onto C57BL/6J (Stock No. 000664) background for at least 4 generations by the donating laboratory. Upon arrival at The Jackson Laboratory, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes.

Allele

Symbol: Vps35^tm1.1Smsa
Name: targeted mutation 1.1, Scott A Small
MGI accession ID: MGI:7327653
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed)
Synonyms: Vps35^fl
Marker symbol: Vps35
Marker name: VPS35 retromer complex component
Marker synonyms: Mem3; PARK17
Chromosome: 8
Strain of origin: (C57BL/6J x 129/Sv)F1
Molecular note: Exons 3 to 5 were floxed and an FRT flanked neo cassette was inserted via homologous recombination. Flp mediated recombination removed the neo cassette.