Strain Name:

B6;129S6-Dnajc5tm1Sud/J

Stock Number:

006392

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Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Type Mutant Stock; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
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Specieslaboratory mouse
Generation?pN1
Generation Definitions
 
Donating InvestigatorDr. Thomas C. Sudhof,   Stanford University School of Medicine

Description
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.

Development
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.

Control Information

  Control
   101045 B6129SF2/J (approximate)
 
  Considerations for Choosing Controls

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

The following phenotype information is associated with a similar, but not exact match to this JAX® Mice strain.

Dnajc5tm1Sud/Dnajc5tm1Sud

        involves: 129S6/SvEvTac
  • mortality/aging
  • premature death
    • began dying in 3rd week post natally and none survived beyond 3 months of age   (MGI Ref ID J:91702)
    • average lifespan is ~62.3 days   (MGI Ref ID J:115193)
  • growth/size/body phenotype
  • decreased body size
    • mice are visibly smaller than littermates at 10 weeks   (MGI Ref ID J:115193)
    • weight loss
      • mice exhibit relative loss of body weight after P20 and   (MGI Ref ID J:115193)
  • postnatal growth retardation
    • weight gain stopped around 15 days of age   (MGI Ref ID J:91702)
  • behavior/neurological phenotype
  • abnormal grip strength
    • in a grip test, mice cannot grip the mesh for very long before dropping, compared to the 2 minute duration of the test achieved by wild-type mice   (MGI Ref ID J:115193)
    • decreased grip strength
      • lack of grip strength   (MGI Ref ID J:91702)
  • abnormal locomotor behavior   (MGI Ref ID J:91702)
    • in a quantitative assessment of motor behavior, mice usually stay in one sector of the force plate and exhibit jerky movements   (MGI Ref ID J:115193)
    • ataxia
      • during motor behavior, mice display severe ataxia and experience sudden falls   (MGI Ref ID J:115193)
    • hypoactivity
      • lack of spontaneous activity in open field tests   (MGI Ref ID J:91702)
    • lethargy
      • became lethargic around 30 days of age but still at and moved about when stimulated   (MGI Ref ID J:91702)
  • abnormal motor coordination/ balance   (MGI Ref ID J:91702)
    • ataxia
      • during motor behavior, mice display severe ataxia and experience sudden falls   (MGI Ref ID J:115193)
    • impaired coordination
      • unable to remain on a turning rod   (MGI Ref ID J:91702)
    • impaired righting response
      • difficulty righting themselves when place on their side by age 15 days and becoming much worse after 25 days of age   (MGI Ref ID J:91702)
      • after postnatal day 20, mice become increasingly debilitated and require up to 30 seconds to become upright   (MGI Ref ID J:115193)
  • abnormal posture   (MGI Ref ID J:91702)
  • decreased startle reflex
    • poor acoustic startle reflex   (MGI Ref ID J:91702)
  • limb grasping
    • tendancy to clasp hindlimbs when suspended by their tail   (MGI Ref ID J:91702)
  • nervous system phenotype
  • abnormal PNS synaptic transmission
    • transmission across the neuromuscular synapse deteriorating by age 20-23 days   (MGI Ref ID J:91702)
    • abnormal endplate potential
      • amplitude of compound muscle action potentials dropped significantly around day 43-47   (MGI Ref ID J:91702)
      • increased synaptic depression due to repetitive stimuli by day 15   (MGI Ref ID J:91702)
      • rise and decay of excitatory post synaptic currents slower and irregular   (MGI Ref ID J:91702)
      • facilitation rather than depression often seen during stimulus trains   (MGI Ref ID J:91702)
      • increased amplitude of currents at day 20-23   (MGI Ref ID J:91702)
  • abnormal neuromuscular synapse morphology
    • neuromuscular junctions with an immature appearance and sometimes lack presynaptic nerve branches   (MGI Ref ID J:91702)
    • appearance indicative of degeneration   (MGI Ref ID J:91702)
    • defects present at all ages but less at 7 days   (MGI Ref ID J:91702)
  • gliosis
    • gliosis resulting from neurodegeneration is prominent in spinal cord and forebrain   (MGI Ref ID J:115193)
    • at P28, strong activation (gliosis) of Muller glia is detected in ONL   (MGI Ref ID J:107310)
  • retinal photoreceptor degeneration   (MGI Ref ID J:107310)
    • mice show considerable photoreceptor degeneration   (MGI Ref ID J:115193)
  • vision/eye phenotype
  • abnormal eye electrophysiology
    • at postnatal day (P)14, a-wave amplitude is reduced to ~40% of littermate controls and exhibits a slower time course; in 4/5 mutants, the b-wave is absent   (MGI Ref ID J:107310)
    • at P18, some mice present with a flat electroretinogram (ERG), while the remainder exhibit small and slow a- and b-waves; mice displaying a measurable ERG response have abnormally slow light responses with the time-to-peak of the a-wave ~3x that of control mice   (MGI Ref ID J:107310)
    • at P30 and P45, all mutants lack a detectable ERG response   (MGI Ref ID J:107310)
  • abnormal retinal outer plexiform layer morphology
    • OPL disintegrates in mutants   (MGI Ref ID J:115193)
    • at P15, presynaptic photoreceptor ribbon terminals are smaller than in wild-type and show an increased synaptic vesicle density; at P28, terminal sizes are heterogeneous, but usually smaller than wild-type, although large swollen terminals are observed with moderate frequency   (MGI Ref ID J:107310)
    • at P28, continuous array of synaptic ribbons in outer plexiform layer (OPL) is disrupted and ectopic ribbons and synaptic proteins are detected in the outer nuclear layer, while membrane attachment of ribbons is decreased; synaptic membrane proteins in OPL are decreased in abundance and nonsynaptic proteins like opsin are mislocalized   (MGI Ref ID J:107310)
    • heterogeneous and pleiomorphic alterations of photoreceptor ribbon synapses such as large decreases in synaptic vesicle density, decrease or loss of the invaginated shape of the presynaptic plasma membrane, formation of electron dense aggregates, detachment or complete loss of synaptic ribbons from presynaptic photoreceptor terminals, are seen at P28   (MGI Ref ID J:107310)
  • abnormal vision   (MGI Ref ID J:115193)
    • on basis of ERG results, mutants initially have some visual function but suffer from a progressive blindness   (MGI Ref ID J:107310)
    • blindness
      • after 4 weeks of age, vision is abolished in mutant mice   (MGI Ref ID J:107310)
  • retinal photoreceptor degeneration   (MGI Ref ID J:107310)
    • mice show considerable photoreceptor degeneration   (MGI Ref ID J:115193)
  • thin retinal outer nuclear layer
    • ONL shrinks dramatically with photoreceptor degeneration   (MGI Ref ID J:115193)
  • muscle phenotype
  • decreased skeletal muscle mass
    • decreased pelvic girdle muscle mass   (MGI Ref ID J:91702)
  • progressive muscle weakness
    • appears by 2-3 weeks of age   (MGI Ref ID J:91702)
  • endocrine/exocrine gland phenotype
  • cryptorchism
    • bilateral abdominal cryptorchism   (MGI Ref ID J:91702)
  • reproductive system phenotype
  • cryptorchism
    • bilateral abdominal cryptorchism   (MGI Ref ID J:91702)
  • hearing/vestibular/ear phenotype
  • *normal* hearing/vestibular/ear phenotype
    • mice display normal morphology and function of presynaptic ribbons in inner hair cells   (MGI Ref ID J:107310)
    • abnormal otoacoustic response
      • at 4 weeks of age, mice show a reduction or loss of otoacoustic emissions   (MGI Ref ID J:107310)
    • impaired hearing
      • at 4 weeks of age, mice show mild hearing impairment of ~30 decibels   (MGI Ref ID J:107310)
      • conductive hearing impairment
        • hearing impairment is presumed to be due in part to a defect in middle ear sound transduction   (MGI Ref ID J:107310)
View Research Applications

Research Applications
This mouse can be used to support research in many areas including:

Neurobiology Research
Neurotransmitter Receptor and Synaptic Vesicle Defects

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Dnajc5tm1Sud
Allele Name targeted mutation 1, Thomas C Sudhof
Allele Type Targeted (Null/Knockout)
Common Name(s) CSP-; CSPalphaKO;
Mutation Made ByDr. Thomas Sudhof,   Stanford University School of Medicine
Strain of Origin129S6/SvEvTac
ES Cell Line NameSM1
ES Cell Line Strain129S6/SvEvTac
Gene Symbol and Name Dnajc5, DnaJ (Hsp40) homolog, subfamily C, member 5
Chromosome 2
Gene Common Name(s) 2610314I24Rik; AU018536; CLN4; CLN4B; CSP; Csp; DNAJC5A; NCL; RIKEN cDNA 2610314I24 gene; cysteine string protein; expressed sequence AU018536;
Molecular Note Exon 1, encoding residues 1-36, was replaced with a neomycin resistance gene. Immunoblot confirmed absence of protein in mutant brains. [MGI Ref ID J:91702]

Genotyping

Genotyping Information

Genotyping Protocols

Dnajc5tm1Sud, Separated PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Fernandez-Chacon R; Wolfel M; Nishimune H; Tabares L; Schmitz F; Castellano-Munoz M; Rosenmund C; Montesinos ML; Sanes JR; Schneggenburger R; Sudhof TC. 2004. The synaptic vesicle protein CSP alpha prevents presynaptic degeneration. Neuron 42(2):237-51. [PubMed: 15091340]  [MGI Ref ID J:91702]

Additional References

Dnajc5tm1Sud related

Burre J; Sharma M; Tsetsenis T; Buchman V; Etherton M; Sudhof TC. 2010. {alpha}-Synuclein Promotes SNARE-Complex Assembly in Vivo and in Vitro. Science :. [PubMed: 20798282]  [MGI Ref ID J:164218]

Chandra S; Gallardo G; Fernandez-Chacon R; Schluter OM; Sudhof TC. 2005. Alpha-synuclein cooperates with CSPalpha in preventing neurodegeneration. Cell 123(3):383-96. [PubMed: 16269331]  [MGI Ref ID J:115193]

Garcia-Junco-Clemente P; Cantero G; Gomez-Sanchez L; Linares-Clemente P; Martinez-Lopez JA; Lujan R; Fernandez-Chacon R. 2010. Cysteine string protein-alpha prevents activity-dependent degeneration in GABAergic synapses. J Neurosci 30(21):7377-91. [PubMed: 20505105]  [MGI Ref ID J:160914]

Kyle BD; Ahrendt E; Braun AP; Braun JE. 2013. The large conductance, calcium-activated K+ (BK) channel is regulated by cysteine string protein. Sci Rep 3:2447. [PubMed: 23945775]  [MGI Ref ID J:207798]

Ninkina N; Peters OM; Connor-Robson N; Lytkina O; Sharfeddin E; Buchman VL. 2012. Contrasting effects of alpha-synuclein and gamma-synuclein on the phenotype of cysteine string protein alpha (CSPalpha) null mutant mice suggest distinct function of these proteins in neuronal synapses. J Biol Chem 287(53):44471-7. [PubMed: 23129765]  [MGI Ref ID J:193755]

Rozas JL; Gomez-Sanchez L; Mircheski J; Linares-Clemente P; Nieto-Gonzalez JL; Vazquez ME; Lujan R; Fernandez-Chacon R. 2012. Motorneurons require cysteine string protein-alpha to maintain the readily releasable vesicular pool and synaptic vesicle recycling. Neuron 74(1):151-65. [PubMed: 22500637]  [MGI Ref ID J:188391]

Ruiz R; Biea IA; Tabares L. 2014. alpha-Synuclein A30P decreases neurodegeneration and increases synaptic vesicle release probability in CSPalpha-null mice. Neuropharmacology 76 Pt A:106-17. [PubMed: 24036317]  [MGI Ref ID J:202023]

Ruiz R; Casanas JJ; Sudhof TC; Tabares L. 2008. Cysteine string protein-alpha is essential for the high calcium sensitivity of exocytosis in a vertebrate synapse. Eur J Neurosci 27(12):3118-31. [PubMed: 18598257]  [MGI Ref ID J:137448]

Schmitz F. 2006. CSP{alpha}-deficiency causes massive and rapid photoreceptor degeneration. Proc Natl Acad Sci U S A 103(8):2926-31. [PubMed: 16477021]  [MGI Ref ID J:107310]

Sharma M; Burre J; Bronk P; Zhang Y; Xu W; Sudhof TC. 2012. CSPalpha knockout causes neurodegeneration by impairing SNAP-25 function. EMBO J 31(4):829-41. [PubMed: 22187053]  [MGI Ref ID J:181971]

Sharma M; Burre J; Sudhof TC. 2012. Proteasome Inhibition Alleviates SNARE-Dependent Neurodegeneration. Sci Transl Med 4(147):147ra113. [PubMed: 22896677]  [MGI Ref ID J:187149]

Zhang YQ; Henderson MX; Colangelo CM; Ginsberg SD; Bruce C; Wu T; Chandra SS. 2012. Identification of CSPalpha clients reveals a role in dynamin 1 regulation. Neuron 74(1):136-50. [PubMed: 22500636]  [MGI Ref ID J:188392]

Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.

Colony Maintenance

Breeding & HusbandryWhen maintained as a live colony, homozygous crosses are used.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2140.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.

    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2782.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.

    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Control Information

  Control
   101045 B6129SF2/J (approximate)
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.
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