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. Visit our online Nomenclature tutorial. Species laboratory mouse Generation N?pN1 Generation Definitions   Donating Investigator Dr. Thomas C. Sudhof,   Stanford University School of Medicine

Description
Approximately half of the double homozygous targeted mutation mice die within days of birth. The surviving mice are subject to severe seizures that start in the second postnatal week then die within the following 2 weeks. Nissl staining of brain tissues revealed no structural abnormalities. No changes were found in the levels of selected synaptic proteins. Neurons experience sustained increases in Ca²⁺-dependent synaptic transmission when two or more action potentials are triggered in succession. Electrophysiological recordings from cultured hippocampal cells exhibit no detectable abnormalities. No protein products from the targeted genes are detected in brain tissue. This mutant mouse strain represents a model that may be useful in studies of synaptic vesicle trafficking in neurons.

Development
Targeting vectors containing a neomycin resistance gene were used to replace exons 2-9 encoding residues 208-559 of Sv2a and exon 1 encoding residues 1-149 of Sv2b. The constructs were electroporated into 129P2/OlaHsd-derived E14.1 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
	100903 B6129PF2/J	(approximate)
Considerations for Choosing Controls

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

Sv2a^tm1Sud/Sv2a⁺ Sv2b^tm1Sud/Sv2b^tm1Sud

        involves: 129P2/OlaHsd * C57BL/6

• normal phenotype
• no abnormal phenotype detected   (MGI Ref ID J:59180)

Sv2a^tm1Sud/Sv2a^tm1Sud Sv2b^tm1Sud/Sv2b^tm1Sud

        involves: 129P2/OlaHsd * C57BL/6

• mortality/aging
• complete postnatal lethality
  • 50% of animals die in the first few days after birth; the remainder die by P21   (MGI Ref ID J:59180)
• behavior/neurological phenotype
• seizures
  • age of onset P8; increasing severity and frequency with age   (MGI Ref ID J:59180)
• nervous system phenotype
• *normal* nervous system phenotype
  • normal brain morphology   (MGI Ref ID J:59180)
• • decreased synaptic depression
    • reduced short-term synaptic depression; 3-5 fold increase during repetitive stimulation   (MGI Ref ID J:59180)
  • seizures
    • age of onset P8; increasing severity and frequency with age   (MGI Ref ID J:59180)

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		Sv2atm1Sud
Allele Name		targeted mutation 1, Thomas C Sudhof
Allele Type		Targeted (knock-out)
Common Name(s)		SV2A-;
Strain of Origin		129P2/OlaHsd
ES Cell Line Name		E14.1
ES Cell Line Strain		129P2/OlaHsd
Gene Symbol and Name		Sv2a, synaptic vesicle glycoprotein 2 a
Chromosome		3
Gene Common Name(s)		AI746429; SV2; expressed sequence AI746429;
Molecular Note		A neomycin resistance cassette replaced a genomic fragment containing exons 2-9. Western blot analysis on brain lysates derived from homozygous mice demonstrated that no detectable protein was expressed from this allele. [MGI Ref ID J:59180]
Allele Symbol		Sv2btm1Sud
Allele Name		targeted mutation 1, Thomas C Sudhof
Allele Type		Targeted (knock-out)
Common Name(s)		SV2B-;
Strain of Origin		129P2/OlaHsd
ES Cell Line Name		E14.1
ES Cell Line Strain		129P2/OlaHsd
Gene Symbol and Name		Sv2b, synaptic vesicle glycoprotein 2 b
Chromosome		7
Gene Common Name(s)		A830038F04Rik; AI850768; HsT19680; RIKEN cDNA A830038F04 gene; expressed sequence AI850768; mKIAA0735;
Molecular Note		A neomycin selection cassette replaced the first coding exon and flanking sequences. Western blot analysis on brain lysates derived from homozygous mice confirmed that no detectable encoded protein was made. [MGI Ref ID J:59180]

Genotyping

Genotyping Information

Genotyping Protocols

Sv2a^tm1Sud, Standard PCR
Sv2b^tm1Sud, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Janz R; Goda Y; Geppert M; Missler M; Sudhof TC. 1999. SV2A and SV2B function as redundant Ca2+ regulators in neurotransmitter release. Neuron 24(4):1003-16. [PubMed: 10624962]  [MGI Ref ID J:59180]

Additional References

Sv2a^tm1Sud related

Chang WP; Sudhof TC. 2009. SV2 renders primed synaptic vesicles competent for Ca2+ -induced exocytosis. J Neurosci 29(4):883-97. [PubMed: 19176798]  [MGI Ref ID J:144830]

Dong M; Yeh F; Tepp WH; Dean C; Johnson EA; Janz R; Chapman ER. 2006. SV2 is the protein receptor for botulinum neurotoxin A. Science 312(5773):592-6. [PubMed: 16543415]  [MGI Ref ID J:108334]

Sv2b^tm1Sud related

Chang WP; Sudhof TC. 2009. SV2 renders primed synaptic vesicles competent for Ca2+ -induced exocytosis. J Neurosci 29(4):883-97. [PubMed: 19176798]  [MGI Ref ID J:144830]

Dong M; Yeh F; Tepp WH; Dean C; Johnson EA; Janz R; Chapman ER. 2006. SV2 is the protein receptor for botulinum neurotoxin A. Science 312(5773):592-6. [PubMed: 16543415]  [MGI Ref ID J:108334]

Lazzell DR; Belizaire R; Thakur P; Sherry DM; Janz R. 2004. SV2B regulates synaptotagmin 1 by direct interaction. J Biol Chem 279(50):52124-31. [PubMed: 15466855]  [MGI Ref ID J:95183]

Wan QF; Zhou ZY; Thakur P; Vila A; Sherry DM; Janz R; Heidelberger R. 2010. SV2 acts via presynaptic calcium to regulate neurotransmitter release. Neuron 66(6):884-95. [PubMed: 20620874]  [MGI Ref ID J:163164]

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 & Husbandry	When maintaining a live colony, mice heterozygous for both mutations may be bred together. Once established, mice heterozygous for the Sv2a mutation and homozygous for Sv2b mutation may be bred together (or to wildtype mice). Mice homozygous for both mutations are not viable.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

Control Information

	Control
	100903 B6129PF2/J	(approximate)
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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The Jackson Laboratory's Genotype Promise

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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