Strain Name:

B6;129S-Stxbp1tm1Sud/J

Stock Number:

006381

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Availability:

Cryopreserved - Ready for recovery

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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
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.

Development
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.

Control Information

  Control
   Wild-type from the colony
   101045 B6129SF2/J (approximate)
 
  Considerations for Choosing Controls

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI
- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested.
Epileptic Encephalopathy, Early Infantile, 4; EIEE4   (STXBP1)
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.

Stxbp1tm1Sud/Stxbp1tm1Sud

        Background Not Specified
  • mortality/aging
  • complete neonatal lethality
    • animals die at birth, probably due to an inability to breathe   (MGI Ref ID J:77237)
  • nervous system phenotype
  • *normal* nervous system phenotype
    • homozygous mice exhibited normal brain development and initial formation of synaptic connections   (MGI Ref ID J:77237)
    • abnormal synaptic transmission
      • no synaptic activity was detectable in embryonic stages in homozygous mice; however, postsynaptic receptors were functional and spontaneous action potentials were observed   (MGI Ref ID J:77237)
      • abnormal neurotransmitter secretion
        • complete loss of neurotransmitter secretion from synaptic vesicles during development   (MGI Ref ID J:77237)
        • cultured neurons lack neurotransmitter synaptic vesicle secretion unlike wild-type cells   (MGI Ref ID J:100337)
    • neurodegeneration
      • apoptotic death of mature neurons was noted starting in the lower brainstem and later in the midbrain and basal forebrain   (MGI Ref ID J:77237)
      • axon degeneration
        • degeneration of the phrenic nerve was noted in homozygous mice; the phrenic nerve initially innervated the diaphragm and the neuromuscular synapse formed normally at E14 -E15, but then degenerated and disappeared by E18   (MGI Ref ID J:85723)
      • neuron degeneration
        • loss of neurons in culture between 3 and 7 DIV without improvement when cultured with wild-type neurons or application of insulin or BDNF   (MGI Ref ID J:100337)
        • however, degeneration is delayed by culturing on glial cells and organoculture with wild-type slices of the hippocampus   (MGI Ref ID J:100337)
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 Stxbp1tm1Sud
Allele Name targeted mutation 1, Thomas C Sudhoff
Allele Type Targeted (knock-out)
Common Name(s) munc18-1-;
Mutation Made ByDr. Thomas Sudhof,   Stanford University School of Medicine
ES Cell Line NameOther (see notes)
Gene Symbol and Name Stxbp1, syntaxin binding protein 1
Chromosome 2
Gene Common Name(s) AI317162; AI326233; ANC18HA; MUNC18-1; Munc-18a; N-sec1; NSEC1; NSEC1A; P67; RBSEC1; Rb-sec1; Sec1; Sxtbp1; UNC18; Unc18-1; Unc18h; expressed sequence AI317162; expressed sequence AI326233; rbSec1A; rbSec1B; unc18 homolog (C. elegans);
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. [MGI Ref ID J:77237]

Genotyping

Genotyping Information

Genotyping Protocols

Stxbp1tm1Sud, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Verhage M; Maia AS; Plomp JJ; Brussaard AB; Heeroma JH; Vermeer H; Toonen RF; Hammer RE; van den Berg TK; Missler M; Geuze HJ; Sudhof TC. 2000. Synaptic assembly of the brain in the absence of neurotransmitter secretion. Science 287(5454):864-9. [PubMed: 10657302]  [MGI Ref ID J:77237]

Additional References

Stxbp1tm1Sud related

Bouwman J; Maia AS; Camoletto PG; Posthuma G; Roubos EW; Oorschot VM; Klumperman J; Verhage M. 2004. Quantification of synapse formation and maintenance in vivo in the absence of synaptic release. Neuroscience 126(1):115-26. [PubMed: 15145078]  [MGI Ref ID J:91381]

Dallman MA; Ladle DR. 2013. Quantitative analysis of locomotor defects in neonatal mice lacking proprioceptive feedback. Physiol Behav 120C:97-105. [PubMed: 23911806]  [MGI Ref ID J:199869]

Deak F; Xu Y; Chang WP; Dulubova I; Khvotchev M; Liu X; Sudhof TC; Rizo J. 2009. Munc18-1 binding to the neuronal SNARE complex controls synaptic vesicle priming. J Cell Biol 184(5):751-64. [PubMed: 19255244]  [MGI Ref ID J:146215]

Heeroma JH; Plomp JJ; Roubos EW; Verhage M. 2003. Development of the mouse neuromuscular junction in the absence of regulated secretion. Neuroscience 120(3):733-44. [PubMed: 12895513]  [MGI Ref ID J:85723]

Heeroma JH; Roelandse M; Wierda K; van Aerde KI; Toonen RF; Hensbroek RA; Brussaard A; Matus A; Verhage M. 2004. Trophic support delays but does not prevent cell-intrinsic degeneration of neurons deficient for munc18-1. Eur J Neurosci 20(3):623-34. [PubMed: 15255974]  [MGI Ref ID J:100337]

Honarpour N; Tabuchi K; Stark JM; Hammer RE; Sudhof TC; Parada LF; Wang X; Richardson JA; Herz J. 2001. Embryonic neuronal death due to neurotrophin and neurotransmitter deprivation occurs independent of Apaf-1. Neuroscience 106(2):263-74. [PubMed: 11566499]  [MGI Ref ID J:85905]

Korteweg N; Maia AS; Verhage M; Burbach JP. 2004. Development of the mouse hypothalamo-neurohypophysial system in the munc18-1 null mutant that lacks regulated secretion. Eur J Neurosci 19(11):2944-52. [PubMed: 15182301]  [MGI Ref ID J:91307]

Manent JB; Demarque M; Jorquera I; Pellegrino C; Ben-Ari Y; Aniksztejn L; Represa A. 2005. A noncanonical release of GABA and glutamate modulates neuronal migration. J Neurosci 25(19):4755-65. [PubMed: 15888651]  [MGI Ref ID J:128882]

Nicol X; Voyatzis S; Muzerelle A; Narboux-Neme N; Sudhof TC; Miles R; Gaspar P. 2007. cAMP oscillations and retinal activity are permissive for ephrin signaling during the establishment of the retinotopic map. Nat Neurosci 10(3):340-7. [PubMed: 17259982]  [MGI Ref ID J:120760]

Oh E; Kalwat MA; Kim MJ; Verhage M; Thurmond DC. 2012. Munc18-1 regulates first-phase insulin release by promoting granule docking to multiple syntaxin isoforms. J Biol Chem 287(31):25821-33. [PubMed: 22685295]  [MGI Ref ID J:188845]

Toonen RF. 2003. Role of Munc18-1 in synaptic vesicle and large dense-core vesicle secretion. Biochem Soc Trans 31(Pt 4):848-50. [PubMed: 12887319]  [MGI Ref ID J:84863]

Toonen RF; Kochubey O; de Wit H; Gulyas-Kovacs A; Konijnenburg B; Sorensen JB; Klingauf J; Verhage M. 2006. Dissecting docking and tethering of secretory vesicles at the target membrane. EMBO J 25(16):3725-37. [PubMed: 16902411]  [MGI Ref ID J:119266]

Toonen RF; Wierda K; Sons MS; de Wit H; Cornelisse LN; Brussaard A; Plomp JJ; Verhage M. 2006. Munc18-1 expression levels control synapse recovery by regulating readily releasable pool size. Proc Natl Acad Sci U S A 103(48):18332-7. [PubMed: 17110441]  [MGI Ref ID J:117152]

Toonen RF; de Vries KJ; Zalm R; Sudhof TC; Verhage M. 2005. Munc18-1 stabilizes syntaxin 1, but is not essential for syntaxin 1 targeting and SNARE complex formation. J Neurochem 93(6):1393-400. [PubMed: 15935055]  [MGI Ref ID J:99424]

Voets T; Toonen RF; Brian EC; de Wit H; Moser T; Rettig J; Sudhof TC; Neher E; Verhage M. 2001. Munc18-1 promotes large dense-core vesicle docking. Neuron 31(4):581-91. [PubMed: 11545717]  [MGI Ref ID J:107685]

Wierda KD; Toonen RF; de Wit H; Brussaard AB; Verhage M. 2007. Interdependence of PKC-dependent and PKC-independent pathways for presynaptic plasticity. Neuron 54(2):275-90. [PubMed: 17442248]  [MGI Ref ID J:122957]

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 heterozygotes are bred with wildtype siblings. 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* $2450.00
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 11 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* $3185.00
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 11 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
   Wild-type from the colony
   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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