These mice carry a targeted mutation of Vps35 (vacuolar protein sorting 35) that contains the D620N mutation in exon 15 that is associated with Parkinson's disease. Sequencing confirms the presence of the point mutation.
Heterozygotes are viable and fertile. It is not known if homozygotes are viable. This strain is currently being characterized. We will modify the strain description if necessary as published results become available.
A targeted vector containing a floxed "mini-cDNA" (splice acceptor, sequence encoding exons 15 through 17, polyadenylation signal), with a FRT site flanked NEO cassette on the 3'end of the mini-cDNA and a third loxP site, was inserted into intron 14-15. The construct was electroporated into C57BL/6 derived Bruce4 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. The resulting chimeric animals were tested for germline transmission. The mice were then crossed to FLP expressing mice on the C57BL/6J genetic background, to remove the NEO cassette. The FLP recombinase transgene was then bred out from the line. The mice were maintained on the C57BL/6 background. Upon arrival at The Jackson Laboratory, the mice (Stock No. 021807) were crossed to C57BL/6J (Stock No. 000664) at least once. The (Stock No. 021807) mice were then crossed to Cre deleter line on the B6 background (Stock No. 008454) to remove the floxed "mini-cDNA" sequence and allow expression of the D620N mutation. The mice were then bred to remove the Cre recombinase allele.
|Allele Name||targeted mutation 1.1,The Michael J Fox Foundation|
|Allele Type||Targeted (Humanized sequence)|
|Allele Synonym(s)||D620N VPS35 KI; VKI; VPS35D620N|
|Gene Symbol and Name||Vps35, VPS35 retromer complex component|
|Strain of Origin||B6.Cg-Thy1a|
|Molecular Note||A targeted vector containing a floxed "mini-cDNA" including a splice acceptor and normal cDNA sequence for exons 15-17, followed by a frt-flanked neo cassette and a third loxP site, inserted into intron 14, and a nucleotide change causing a D620N mutation in the inherent mouse gene sequence 3' of the insertion. The polyadenylation signal sequence at the end of the mini-cDNA prevents expression of the D620N mutation. Flp-mediated recombination removed the neo cassette. Cre-mediated recombination removed the "mini-cDNA" sequence and allows expression of the D620N mutation.|
When maintaining a live colony, heterozygous mice may be bred together, to wildtype siblings, or to C57BL/6J inbred mice (Stock No. 000664). It is not known if homozygotes are viable.
When using the B6(Cg)-Vps35tm1.1Mjff/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #023409 in your Materials and Methods section.