Homozygous syntaxin binding protein 1 ( Stxbp1, formerly munc18-1) knock-out mice exhibit neurodegeneration and post-natal death.
Dr. Thomas C. Sudhof, Stanford University School of Medicine
Mice homozygous for this targeted mutation die immediately after birth, probably due to respiratory failure. Predicted Mendelian genotypic ratios are demonstrated in progeny of heterozygous crosses. Homozygotes show a complete loss of neurotransmitter secretion from synaptic vesicles throughout development. Postsynaptic receptors are functional and spontaneous action potentials are occasionally observed, however. Ion channels show normal properties. Normal brain assembly, including formation of layered structures, fiber pathways and morphologically defined synapses occurs. After assembly is completed, neurons undergo apoptosis, leading to widespread neurodegeneration. No protein product from the targeted gene is detected in E18 embryos or perinatal pups. This mutant mouse strain represents a model that may be useful in studies of synaptic vesicle exocytosis and neurodegeneration.
A targeting vector containing a neomycin resistance gene was used to replace 5 exons encoding residues 14-29, 30-56, 57-82, 83-108, and 109-144 of the gene. The construct was electroporated into 129/Sv-derived “G-cells” (embryonic stem (ES) cells). Correctly targeted ES cells were injected into C57BL/6 blastocysts. Chimeric animals were crossed with C57BL/6. The strain has been minimally backcrossed to C57BL/6 by the donating laboratory.
|Allele Name||targeted mutation 1, Thomas C Sudhoff|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Stxbp1, syntaxin binding protein 1|
|Strain of Origin||Not Specified|
|General Note||The targeting vector was electroporated into "G-cell" ES cells.|
|Molecular Note||Five exons, encoding amino acids 14 through 144, were replaced with a neomycin selection cassette. Neither transcript nor protein was detected in homozygous mice by Northern blot or Western blot analyses.|
|Mutations Made By|| |
Dr. Thomas Sudhof, Stanford University School of Medicine
When maintained as a live colony heterozygotes are bred with wildtype siblings. Homozygotes are not viable.
When using the munc18-1 KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #006381 in your Materials and Methods section.
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