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. Species laboratory mouse Generation ?+N1p (13-MAR-05) Generation Definitions   Donating Investigator Michael 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

Additional Web Information

Genetic Quality Control Annual Report

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

Snap25^tm1Mcw/Snap25^tm1Mcw

        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 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:

Snap25^tm1Mcw 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 (knock-out)
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; 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

Snap25^tm1Mcw, 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]

Snap25^tm1Mcw 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]

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]

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]

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, RG10/RG30.

Colony Maintenance

Breeding & Husbandry	This 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.

Purchasing information

Pricing, Supply Level & Notes, Controls

General Supply Notes

• This strain is included in the Induced Mutant Resource Colony collection.
• Genomic DNA is available for this strain from the Mouse DNA Resource.

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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