These Dnajc5 knock-out mice exhibit neurodegeneration and are useful in studies relating to synaptic transmission.
Dr. Thomas C. Sudhof, Stanford University School of Medicine
Newborn homozygotes with this targeted mutation are viable, normal in size, and do not display any gross physical or behavioral abnormalities. After 15 days of age, the animals stop gaining weight. They rapidly develop a neurodegenerative phenotype which impairs productivity. Young homozygotes show no significant changes in presynaptic Ca2+ currents or synaptic vesicle exocytosis, but at 2-4 weeks of age, these mice develop a progressive, fatal sensorimotor disorder. Neuromuscular junctions and Calyx synapses exhibit increasing neurodegenerative changes, and synaptic transmission becomes severely impaired. Partial paralysis and loss of neuromuscular control are seen by ~20 days of age and most die by 60 days of age (none survive beyond 3 months). No protein product from the targeted gene is detected in brain tissue. This mutant mouse strain represents a model that may be useful in studies of synaptic vesicle transport mechanisms and neurodegeneration.
A targeting vector containing a neomycin resistance gene was used to replace exon 1 (residues 1-36) of the gene. The construct was electroporated into 129S6/SvEvTac-derived SM1embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts.
|Allele Name||targeted mutation 1, Thomas C Sudhof|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||CSP-; Cspa-; CSPalphaKO|
|Gene Symbol and Name||Dnajc5, DnaJ heat shock protein family (Hsp40) member C5|
|Strain of Origin||129S6/SvEvTac|
|Molecular Note||Exon 1, encoding residues 1-36, was replaced with a neomycin resistance gene. Immunoblot confirmed absence of protein in mutant brains.|
|Mutations Made By|| |
Dr. Thomas Sudhof, Stanford University School of Medicine
When maintained as a live colony, homozygous crosses are used.
When using the CSPα KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #006392 in your Materials and Methods section.
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