STOCK Snta1^tm1Scf/J

Stock number: 012940
Product name: α-Syn^-
Research areas: Developmental Biology Research, Neurobiology Research

Description

These Snta1 knock-out mice may be useful for studying synapse formation and maintenance, and the organization of utrophin, acetylcholine receptor, and acetylcholinesterase at neuromuscular junctions.

Detailed description

In this strain, exon 1 of the endogenous mouse syntrophin, acidic 1 (Snta1) gene is replaced with a neo cassette abolishing gene function. Mice homozygous for the Snta1 allele are viable and fertile. Homozygotes tend to be small at 3 weeks of age and the Donating Investigator reports weaning the mice at 4 weeks. Neuromuscular junctions in homozygous Snta1^-/- mice have undetectable levels of postsynaptic utrophin, reduced levels of acetylcholine receptor and acetylcholinesterase, shallow nerve gutters, abnormal distributions of acetylcholine receptors, and postjunctional folds that are generally less organized and have fewer openings to the synaptic cleft than controls. Snta1^-/- mice also exhibit a mislocalization of the water channel aquaporin-4 (AQP4) at the blood-brain barrier leading to reduced edema and infarct volume in brain trauma models, and reduced K+ clearance from the neuropil leading to increased seizure and stroke susceptibility. These mice may be useful for studying synapse formation and maintenance, and the organization of utrophin, acetylcholine receptor, and acetylcholinesterase at neuromuscular junctions, and water homeostasis in the brain.

Development

A targeting vector was designed to replace exon 1 of the syntrophin, acidic 1 (Snta1) gene with a neomycin resistance (neo) cassette. The construct was electroporated into 129P2/OlaHsd-derived E14 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts and the resulting chimeric males were bred to C57BL/6J females. These mice were subsequently backcrossed for at least 10 generations to C57BL/6J background (see SNP note below) to generate a colony of Snta1^-/- mice. Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J (Stock No. 000664) for at least one generation to establish the colony.

A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. At least 6 the 32 markers on 6 chromosomes were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a mixed genetic background.

Allele

Symbol: Snta1^tm1Scf
Name: targeted mutation 1, Stanley C Froehner
MGI accession ID: MGI:2179769
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Snta1
Marker name: syntrophin, acidic 1
Chromosome: 2
Strain of origin: 129P2/OlaHsd
Expressed genes: neo,neomycin resistance,bacterial
Molecular note: A neomycin resistance cassette replaced a genomic fragment containing exon 1, which encodes the first 97 amino acids including part of the PH domain and part of the PDZ domain. Northern blot analysis on RNA derived from skeletal muscle of homozygous mice demonstrated that aberrant transcripts were expressed from this allele, but immunoprecipitation experiments confirmed that no detectable encoded protein was present in skeletal muscle of homozygous mice.