Strain Name:

B6.129X1-Snap25tm1Mcw/J

Stock Number:

004863

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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 Congenic; Mutant Strain; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Additional information on Congenic nomenclature.
Specieslaboratory mouse
 
Donating Investigator Michael C. Wilson,   University of New Mexico

Description
Homozygous mutant mice die at birth from respiratory failure. At embryonic day 17.5 to 18.5 homozygous embryos appear smaller and do not display spontaneous movement or sensorimotor reflexes. Dilated vascular channels in subcutaneous tissues give the embryos an external blotchy appearance. No gene product (mRNA or protein) is detected by Northern or Western blot analysis of brain tissue from homozygous animals. Histological analysis of fetal diaphragm tissue reveals a dispersed pattern of innervation and fewer layers of muscle fibers. Thin, disarrayed intercostal and anterior chestwall muscles are also observed. Spontaneous miniature endplate potential (mEPP) activity is detected in the diaphragm phrenic nerve, but no evoked endplate potentials (EPP), evoked neurotransmitter release or muscle contraction is detected with stimulation of the neuromuscular junction (NMJ). Mutant NMJs exhibit larger endplate diameters and lower levels of acetylcholinesterase. Tetrodotoxin (TTX) resistant miniature excitatory postsynaptic currents (mEPSCs), but not evoked, action-potential dependent responses are detected from mutant central nervous system (CNS) synapses. Mice that are heterozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. Thismutant mouse strain may be useful in studies of neuroexocytosis and neurotransmitter release in the developing nervous system.

Development
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt exons 5a and 5b and part of the downstream intron. The construct was electroporated into 129X1/SvJ derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric animals were crossed to C57BL/6 mice, and then backcrossed to C57BL/6 for 7 generations (September 2003).

Control Information

  Control
   See control note: Wildtype mice from the colony or C57BL/6J mice (Stock No. 000664) may be used as controls.
   Wild-type from the colony
   000664 C57BL/6J
 
  Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Snap25
021879   B6.Cg-Snap25tm1.1Hze/J
023525   B6;129S-Snap25tm2.1(cre)Hze/J
018067   FVB-Tg(Prism)1849Htz/J
018071   FVB-Tg(Prism)1861Htz/J
018068   FVB-Tg(Prism)1989Htz/J
View Strains carrying other alleles of Snap25     (5 strains)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

Snap25tm1Mcw/Snap25tm1Mcw

        involves: C57BL/6
  • mortality/aging
  • complete neonatal lethality
    • lethality at birth is suggested to be due to respiratory failure   (MGI Ref ID J:73755)
  • behavior/neurological phenotype
  • no spontaneous movement
    • no movement was detectable in response to mechanical stimuli   (MGI Ref ID J:73755)
  • unresponsive to tactile stimuli   (MGI Ref ID J:73755)
  • cardiovascular system phenotype
  • abnormal blood vessel morphology
    • dilated vascular channels are found in the subcutaneous soft tissue resulting in hyperemic skin blotches   (MGI Ref ID J:73755)
  • embryogenesis phenotype
  • decreased embryo size
    • homozygous animals appear smaller and exhibit a tucked position   (MGI Ref ID J:73755)
  • growth/size/body phenotype
  • decreased embryo size
    • homozygous animals appear smaller and exhibit a tucked position   (MGI Ref ID J:73755)
  • muscle phenotype
  • abnormal intercostal muscle morphology
    • thin and disorganized musculature and AChR cluster sites are more dispersed in mutant muscles   (MGI Ref ID J:73755)
  • thin diaphragm muscle
    • thin and disorganized musculature and AChR cluster sites are more dispersed in mutant muscles   (MGI Ref ID J:73755)
  • respiratory system phenotype
  • respiratory failure
    • at birth, animals do not breathe   (MGI Ref ID J:73755)
  • nervous system phenotype
  • abnormal CNS synaptic transmission   (MGI Ref ID J:73755)
    • abnormal miniature excitatory postsynaptic currents
      • spontaneous miniature excitatory postsynaptic currents (mEPSCs) were detected in mutant hippocampal neurons, but the frequency was lower than in controls; treatment of neurons with agents to accelerate vesicle fusion events increased this frequency   (MGI Ref ID J:73755)
      • neuronal postsynaptic responses were unaffected   (MGI Ref ID J:73755)
      • the transmission defect is suggested to be due to a block in regulated presynaptic exocytosis   (MGI Ref ID J:73755)
  • abnormal PNS synaptic transmission   (MGI Ref ID J:73755)
    • abnormal endplate potential
      • phrenic nerve stimulation of mutant diaphragms resulted in absence of EPPs and evoked contractility; however, carbachol treatment resulted in contraction of mutant diaphragms suggesting that the muscles are capable of responding to neurotransmitter signals   (MGI Ref ID J:73755)
      • spontaneous miniature EPP activity was recorded in mutant diaphragms due to low spontaneous release of acetylcholine   (MGI Ref ID J:73755)
  • abnormal brain morphology   (MGI Ref ID J:80415)
    • abnormal cerebral cortex morphology
      • abnormal neocortical plate morphology; irregular bulges and undulations in the cortical plate in a subset of mutant animals   (MGI Ref ID J:80415)
  • integument phenotype
  • abnormal skin condition   (MGI Ref ID J:73755)
  • blotchy skin
    • dilated vascular channels are found in the subcutaneous soft tissue resulting in hyperemic skin blotches   (MGI Ref ID J:73755)
  • unresponsive to tactile stimuli   (MGI Ref ID J:73755)
View Research Applications

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

Snap25tm1Mcw related

Cardiovascular Research
Vascular Defects

Developmental Biology Research
Growth Defects
      Growth Defects (homozygous)
Perinatal Lethality
      Homozygous

Neurobiology Research
Neuromuscular Defects

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Snap25tm1Mcw
Allele Name targeted mutation 1, Michael C Wilson
Allele Type Targeted (Null/Knockout)
Common Name(s) Snap25-;
Mutation Made By Michael Wilson,   University of New Mexico
Gene Symbol and Name Snap25, synaptosomal-associated protein 25
Chromosome 2
Gene Common Name(s) Bdr; GENA 70; RIC-4; RIC4; SEC9; SNAP; SNAP-25; SNAP-25B; SNAP-25a; bA416N4.2; blind drunk; dJ1068F16.2; sp;
Molecular Note Exon 5a/b and part of the downstream intron were replaced with a PGK-neo cassette by homologous recombination. Western blot of brain proteins and RT-PCR analysis of total brain RNA from homozygous mutant embryos verified the absence of gene expression. [MGI Ref ID J:73755]

Genotyping

Genotyping Information

Genotyping Protocols

Snap25tm1Mcw, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Washbourne P; Thompson PM; Carta M; Costa ET; Mathews JR; Lopez-Bendito G; Molnar Z; Becher MW; Valenzuela CF; Partridge LD; Wilson MC. 2002. Genetic ablation of the t-SNARE SNAP-25 distinguishes mechanisms of neuroexocytosis. Nat Neurosci 5(1):19-26. [PubMed: 11753414]  [MGI Ref ID J:73755]

Additional References

Molnar Z; Lopez-Bendito G; Small J; Partridge LD; Blakemore C; Wilson MC. 2002. Normal development of embryonic thalamocortical connectivity in the absence of evoked synaptic activity. J Neurosci 22(23):10313-23. [PubMed: 12451131]  [MGI Ref ID J:80415]

Snap25tm1Mcw related

Bark C; Bellinger FP; Kaushal A; Mathews JR; Partridge LD; Wilson MC. 2004. Developmentally regulated switch in alternatively spliced SNAP-25 isoforms alters facilitation of synaptic transmission. J Neurosci 24(40):8796-805. [PubMed: 15470145]  [MGI Ref ID J:94005]

Blakey D; Wilson MC; Molnar Z. 2012. Termination and initial branch formation of SNAP-25-deficient thalamocortical fibres in heterochronic organotypic co-cultures. Eur J Neurosci 35(10):1586-94. [PubMed: 22607004]  [MGI Ref ID J:207667]

Bronk P; Deak F; Wilson MC; Liu X; Sudhof TC; Kavalali ET. 2007. Differential effects of SNAP-25 deletion on Ca2+ -dependent and Ca2+ -independent neurotransmission. J Neurophysiol 98(2):794-806. [PubMed: 17553942]  [MGI Ref ID J:147690]

Mohrmann R; de Wit H; Verhage M; Neher E; Sorensen JB. 2010. Fast vesicle fusion in living cells requires at least three SNARE complexes. Science 330(6003):502-5. [PubMed: 20847232]  [MGI Ref ID J:165422]

Molnar Z; Higashi S; Lopez-Bendito G. 2003. Choreography of early thalamocortical development. Cereb Cortex 13(6):661-9. [PubMed: 12764042]  [MGI Ref ID J:102089]

Molnar Z; Lopez-Bendito G; Small J; Partridge LD; Blakemore C; Wilson MC. 2002. Normal development of embryonic thalamocortical connectivity in the absence of evoked synaptic activity. J Neurosci 22(23):10313-23. [PubMed: 12451131]  [MGI Ref ID J:80415]

Nagy G; Milosevic I; Fasshauer D; Muller EM; de Groot BL; Lang T; Wilson MC; Sorensen JB. 2005. Alternative splicing of SNAP-25 regulates secretion through nonconservative substitutions in the SNARE domain. Mol Biol Cell 16(12):5675-85. [PubMed: 16195346]  [MGI Ref ID J:107104]

Nouvian R; Neef J; Bulankina AV; Reisinger E; Pangrsic T; Frank T; Sikorra S; Brose N; Binz T; Moser T. 2011. Exocytosis at the hair cell ribbon synapse apparently operates without neuronal SNARE proteins. Nat Neurosci 14(4):411-3. [PubMed: 21378973]  [MGI Ref ID J:172303]

Oliver PL; Davies KE. 2009. Interaction between environmental and genetic factors modulates schizophrenic endophenotypes in the Snap-25 mouse mutant blind-drunk. Hum Mol Genet 18(23):4576-89. [PubMed: 19729413]  [MGI Ref ID J:153982]

Pozzi D; Condliffe S; Bozzi Y; Chikhladze M; Grumelli C; Proux-Gillardeaux V; Takahashi M; Franceschetti S; Verderio C; Matteoli M. 2008. Activity-dependent phosphorylation of Ser187 is required for SNAP-25-negative modulation of neuronal voltage-gated calcium channels. Proc Natl Acad Sci U S A 105(1):323-8. [PubMed: 18162553]  [MGI Ref ID J:131023]

Raingo J; Khvotchev M; Liu P; Darios F; Li YC; Ramirez DM; Adachi M; Lemieux P; Toth K; Davletov B; Kavalali ET. 2012. VAMP4 directs synaptic vesicles to a pool that selectively maintains asynchronous neurotransmission. Nat Neurosci 15(5):738-45. [PubMed: 22406549]  [MGI Ref ID J:191257]

Scullin CS; Tafoya LC; Wilson MC; Partridge LD. 2012. Presynaptic residual calcium and synaptic facilitation at hippocampal synapses of mice with altered expression of SNAP-25. Brain Res 1431:1-12. [PubMed: 22119397]  [MGI Ref ID J:178992]

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]

Tafoya LC; Mameli M; Miyashita T; Guzowski JF; Valenzuela CF; Wilson MC. 2006. Expression and function of SNAP-25 as a universal SNARE component in GABAergic neurons. J Neurosci 26(30):7826-38. [PubMed: 16870728]  [MGI Ref ID J:111062]

Weber JP; Reim K; Sorensen JB. 2010. Opposing functions of two sub-domains of the SNARE-complex in neurotransmission. EMBO J 29(15):2477-90. [PubMed: 20562829]  [MGI Ref ID J:163403]

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 & HusbandryThis strain originated on a B6;129 background and was backcrossed to C57BL/6 for 7 generations (September 2003). The strain must be maintained as a heterozygote. Homozygotes are not viable.

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* $2525.00
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.

Frozen Products

Price (US dollars $)
Frozen Embryo $1650.00

Standard Supply

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

Supply Notes

  • Cryopreserved Embryos
    Available to most shipping destinations1
    This strain is also available as cryopreserved embryos2. Orders for cryopreserved embryos may be placed with our Customer Service Department. Experienced technicians at The Jackson Laboratory have recovered frozen embryos of this strain successfully. We will provide you enough embryos to perform two embryo transfers. The Jackson Laboratory does not guarantee successful recovery at your facility. For complete information on purchasing embryos, please visit our Cryopreserved Embryos web page.

    1 Shipments cannot be made to Australia due to Australian government import restrictions.
    2 Embryos for most strains are cryopreserved at the two cell stage while some strains are cryopreserved at the eight cell stage. If this information is important to you, please contact Customer Service.
  • 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* $3283.00
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.

Frozen Products

Price (US dollars $)
Frozen Embryo $2145.00

Standard Supply

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

Supply Notes

  • Cryopreserved Embryos
    Available to most shipping destinations1
    This strain is also available as cryopreserved embryos2. Orders for cryopreserved embryos may be placed with our Customer Service Department. Experienced technicians at The Jackson Laboratory have recovered frozen embryos of this strain successfully. We will provide you enough embryos to perform two embryo transfers. The Jackson Laboratory does not guarantee successful recovery at your facility. For complete information on purchasing embryos, please visit our Cryopreserved Embryos web page.

    1 Shipments cannot be made to Australia due to Australian government import restrictions.
    2 Embryos for most strains are cryopreserved at the two cell stage while some strains are cryopreserved at the eight cell stage. If this information is important to you, please contact Customer Service.
  • 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
   See control note: Wildtype mice from the colony or C57BL/6J mice (Stock No. 000664) may be used as controls.
   Wild-type from the colony
   000664 C57BL/6J
 
  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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