B6;129-Amph^tm1Pdc/J

Stock number: 008514
Research areas: Developmental Biology Research, Neurobiology Research

Description

Amphiphysin (Amph) targeted mutation mice have defects in synaptic vesicle recycling that are unmasked by stimulation suggest impairments at multiple stages of the cycle. These defects correlate with increased mortality due to rare irreversible seizures. Due to such seizures, animals die mainly between two and five months of age without other noticeable health problems. Approximately 50% of homozygotes survive to 10 months of age. Homozygotes exhibit major learning deficits.

Detailed description

In addition to ablated activity of the targeted gene, these mice show a parallel dramatic reduction in amphiphysin 2 selectivity in the brain due to its enhanced degradation in the absence of amphiphysin 1. Defects in synaptic vesicle recycling that are unmasked by stimulation suggest impairments at multiple stages of the cycle. These defects correlate with increased mortality due to rare irreversible seizures. Due to such seizures, animals die mainly between two and five months of age without other noticeable health problems. Approximately 50% of homozygotes survive to 10 months of age. Homozygotes exhibit major learning deficits as demonstrated by the Morris water maze task, and show very mild fear responses in both the context test and the auditory cue test compared to their wild-type littermates. Viable homozygotes reportedly breed until about three months of age and produce small litters of just two to three pups.

Development

A targeting vector was used to replace most of the 3' end of the first coding exon and a fragment of the following intron with PGK-neomycin resistance cassette placed in the same transcriptional orientation as the gene. The targeting vector was introduced to an 129SV/J agouti-derived embryonic stem (ES) cell line. Chimeras were bred to C57BL/6 by the donating laboratory (specific backcross generation unknown).

Allele

Symbol: Amph^tm1Pdc
Name: targeted mutation 1, Pietro De Camilli
MGI accession ID: MGI:2388118
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Amph
Marker name: amphiphysin
Chromosome: 13
Strain of origin: 129/Sv
Molecular note: Exon 1 was disrupted by the insertion of a neomycin selection cassette. Protein was undetected by Western blot analysis and immunofluorescence staining.