STOCK Vapb^tm1.2Ics/J

Stock number: 023592
Product name: Vapb-
Research areas: Cell Biology Research, Neurobiology Research, Research Tools

Description

These Vspb^-/- mice may be useful for studying risk factors for motor neuron diseases such as amyotrophic lateral sclerosis (ALS).

Detailed description

These Vspb^-/- mutant mice lack exon 3 of the vesicle-associated membrane protein, associated protein B and C (Vapb) gene, abolishing gene expression. Vspb encodes a membrane protein involved in vesicle trafficking, membrane fusion, protein complex assembly, and cell motility. Mutations and loss of VAPB function have been shown to contribute to motor deficits associated with amyotrophic lateral sclerosis (ALS) pathogenesis. Homozygotes are viable and fertile. Adult Vapb KO mice develop mild, late onset central nervous system defects including mild motor deficits after 18 months of age and mild tremors in open field tests. These mice do not exhibit defects in neuromuscular junction or muscle strength, and there is no apparent muscle denervation.

Development

A targeting vector was designed to insert a loxP site upstream of exon 3, and a second loxP site followed by a frt-flanked PGK-neo cassette just downstream of exon 3 of the vesicle-associated membrane protein, associated protein B and C (Vapb) gene. The construct was electroporated into 129S2/SvPas-derived P1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and resulting chimeric males were bred to mice expressing Frt-recombinase to remove the neo cassette. Offspring were crossed to remove the Frt-containing transgene and progeny were bred to CMV-cre transgenic mice to remove the floxed-sequence. Subsequently, these Vspb^-/- mice were bred to C57BL/6NTac mice once and were maintained on a mixed background. Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6NJ (Stock No. 005304) for two generations to establish the colony.

Allele

Symbol: Vapb^tm1.2Ics
Name: targeted mutation 1.2, Mouse Clinical Institute
MGI accession ID: MGI:5521564
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Vapb
Marker name: vesicle-associated membrane protein, associated protein B and C
Chromosome: 2
Strain of origin: 129S2/SvPas
Molecular note: Cre-mediated recombination removed a floxed neomycin resistance cassette. Flp-mediated recombination removed the FRT-flanked neomycin resistance cassette. Western blot anlaysis confirmed the absence of protein expression in the cerebral cortex.