Strain Name:

B6;129S2-Slc17a8tm1Edw/J

Stock Number:

016931

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Availability:

Repository- Live

Use Restrictions Apply, see Terms of Use
An EGFP sequence knocked into exon 2 of Slc17a8 abolishes gene function in these mice. Useful applications include studying the role of glutamate transporters in the nervous and auditory systems.

Description

Strain Information

Former Names B6.129P2(Cg)-Slc17a8tm1Edw/J    (Changed: 28-JUN-12 )
Type Mutant Stock; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
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Mating SystemHomozygote x Homozygote         (Female x Male)   12-JUN-13
Specieslaboratory mouse
Generation?+F4 (10-DEC-13)
Generation Definitions
 
Donating Investigator Robert Edwards,   UCSF

Description
An enhanced green fluorescent protein (EGFP) replaces most of exon 2 of the solute carrier family 17, member 8 (Slc17a8 or Vglut3) gene in these mice. Gene function is abolished. EGFP signal is not detected. Homozygotes are viable, fertile, and normal in size. VGLUT3 is a vesicular glutamate transporter that mediates synaptic transmission by transporting the neurotransmitter, glutamate, into secretory vesicles. In wildtype mice, VGLUT3 is expressed by inner hair cells of the cochlea, by serotonergic neurons, cholinergic neurons, a particular subset of primary sensory afferents (low-threshold mechanoreceptors), a subset of GABAergic interneurons, and a variety of other cell populations, some not known to use glutamate as a transmitter. These VGLUT3 deficient mice are deaf and exhibit epileptic seizures with little change in motor behavior.

Development
A targeting vector was designed to replace most of exon 2 encoding the solute carrier family 17, member 8 (Slc17a8 or Vglut3) gene with an enhanced green fluorescent protein (EGFP) followed by a polyadenylation signal and a floxed-neomycin resistance (neo) cassette. The construct was electroporated into 129P2/Ola-derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and the resulting chimeric males were bred to C57BL/6 females. Heterozygous offspring were subsequently bred to mice expressing ACTB-cre to delete the neo cassette. The donating investigator reported that these mice were backcrossed at least 10 generations to C57BL/6 background (see SNP note below). Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J (Stock No. 000664) for at least one generation to establish the colony.

A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. 6 of the 27 markers throughout the genome were segregating between B6J and 129, suggesting an incomplete backcross.

Control Information

  Control
   000664 C57BL/6J (approximate)
 
  Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Slc17a8
018148   STOCK Tg(Slc17a8-EGFP)1Edw/SealJ
018147   STOCK Tg(Slc17a8-icre)1Edw/SealJ
View Strains carrying other alleles of Slc17a8     (2 strains)

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.
Deafness, Autosomal Dominant 25; DFNA25   (SLC17A8)
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.

Slc17a8tm1Edw/Slc17a8+

        involves: 129P2/OlaHsd * C57BL/6
  • nervous system phenotype
  • abnormal brain wave pattern
    • mice exhibit interictal epileptiform abnormalities but no detectable electrographic seizure   (MGI Ref ID J:132704)

Slc17a8tm1Edw/Slc17a8tm1Edw

        involves: 129P2/OlaHsd * C57BL/6
  • nervous system phenotype
  • abnormal brain wave pattern
    • mice exhibit frequent interictal spike discharges   (MGI Ref ID J:132704)
  • abnormal inner hair cell synaptic ribbon morphology
    • 26 of 31 inner cell synapses exhibit abnormally thin, elongated ribbons   (MGI Ref ID J:132704)
  • cochlear ganglion degeneration
    • mice exhibit progressive neuron loss at all levels of the cochlea that is apparent by P10   (MGI Ref ID J:132704)
  • decreased synaptic glutamate release
    • mice do not exhibit no synaptic response in the inner hair cell afferent terminals even when depolarized by elevated potassium   (MGI Ref ID J:132704)
  • nonconvulsive seizures
    • mice exhibit intermittent spontaneous cortical seizures lasting up to 2 minutes   (MGI Ref ID J:132704)
    • however, mice do not display any behavioral abnormalities   (MGI Ref ID J:132704)
  • hearing/vestibular/ear phenotype
  • abnormal inner hair cell synaptic ribbon morphology
    • 26 of 31 inner cell synapses exhibit abnormally thin, elongated ribbons   (MGI Ref ID J:132704)
  • deafness   (MGI Ref ID J:132704)
  • increased or absent threshold for auditory brainstem response   (MGI Ref ID J:132704)
  • sensorineural hearing loss   (MGI Ref ID J:132704)
  • behavior/neurological phenotype
  • absent startle reflex
    • mice do not startle to a loud clap   (MGI Ref ID J:132704)
    • however, motor and vestibular functions are normal   (MGI Ref ID J:132704)
  • nonconvulsive seizures
    • mice exhibit intermittent spontaneous cortical seizures lasting up to 2 minutes   (MGI Ref ID J:132704)
    • however, mice do not display any behavioral abnormalities   (MGI Ref ID J:132704)
View Research Applications

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

Developmental Biology Research
Neurodevelopmental Defects

Neurobiology Research
Channel and Transporter Defects
Epilepsy
Hearing Defects
Neurotransmitter Receptor and Synaptic Vesicle Defects

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Slc17a8tm1Edw
Allele Name targeted mutation 1, Robert H Edwards
Allele Type Targeted (knock-out)
Common Name(s) VGLUT3-;
Mutation Made By Robert Edwards,   UCSF
Strain of Origin129P2/OlaHsd
Gene Symbol and Name Slc17a8, solute carrier family 17 (sodium-dependent inorganic phosphate cotransporter), member 8
Chromosome 10
Gene Common Name(s) BC042593; DFNA25; VGLUT3; cDNA sequence BC042593;
Molecular Note Most of exon 2 was replaced with an EGFP cassette, with a stop codon and poly-adenylation signal, and floxed neo cassette. Germ-line, cre-mediated recombination was used to remove the neo cassette. The absence of protein product was confirmed by western blot analysis on brain extracts. However, no EGFP signal was detected. [MGI Ref ID J:132704]

Genotyping

Genotyping Information

Genotyping Protocols

Slc17a8tm1Edw, Separated PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Seal RP; Akil O; Yi E; Weber CM; Grant L; Yoo J; Clause A; Kandler K; Noebels JL; Glowatzki E; Lustig LR; Edwards RH. 2008. Sensorineural deafness and seizures in mice lacking vesicular glutamate transporter 3. Neuron 57(2):263-75. [PubMed: 18215623]  [MGI Ref ID J:132704]

Additional References

Slc17a8tm1Edw related

Akil O; Seal RP; Burke K; Wang C; Alemi A; During M; Edwards RH; Lustig LR. 2012. Restoration of hearing in the VGLUT3 knockout mouse using virally mediated gene therapy. Neuron 75(2):283-93. [PubMed: 22841313]  [MGI Ref ID J:188349]

Blankenship AG; Ford KJ; Johnson J; Seal RP; Edwards RH; Copenhagen DR; Feller MB. 2009. Synaptic and extrasynaptic factors governing glutamatergic retinal waves. Neuron 62(2):230-41. [PubMed: 19409268]  [MGI Ref ID J:157363]

Noh J; Seal RP; Garver JA; Edwards RH; Kandler K. 2010. Glutamate co-release at GABA/glycinergic synapses is crucial for the refinement of an inhibitory map. Nat Neurosci 13(2):232-8. [PubMed: 20081852]  [MGI Ref ID J:156675]

Seal RP; Wang X; Guan Y; Raja SN; Woodbury CJ; Basbaum AI; Edwards RH. 2009. Injury-induced mechanical hypersensitivity requires C-low threshold mechanoreceptors. Nature 462(7273):651-5. [PubMed: 19915548]  [MGI Ref ID J:155581]

Shields SD; Ahn HS; Yang Y; Han C; Seal RP; Wood JN; Waxman SG; Dib-Hajj SD. 2012. Nav1.8 expression is not restricted to nociceptors in mouse peripheral nervous system. Pain 153(10):2017-30. [PubMed: 22703890]  [MGI Ref ID J:190164]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX18

Colony Maintenance

Breeding & HusbandryWhen maintaining a live colony, homozygous mice may be bred together.
Mating SystemHomozygote x Homozygote         (Female x Male)   12-JUN-13

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


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

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $232.00Female or MaleHomozygous for Slc17a8tm1Edw  
Price per Pair (US dollars $)Pair Genotype
$464.00Homozygous for Slc17a8tm1Edw x Homozygous for Slc17a8tm1Edw  

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1500 unique mouse models across a vast array of research areas. Breeding colonies provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. If a Repository strain is not immediately available, then within 2 to 3 business days, you will receive an estimated availability timeframe for your inquiry or order along with various delivery options. Repository strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping. We will note and try to accommodate requests for specific ages of Repository strains but cannot guarantee provision of these strains at specific ages. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, please let us know.

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $301.60Female or MaleHomozygous for Slc17a8tm1Edw  
Price per Pair (US dollars $)Pair Genotype
$603.20Homozygous for Slc17a8tm1Edw x Homozygous for Slc17a8tm1Edw  

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1500 unique mouse models across a vast array of research areas. Breeding colonies provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. If a Repository strain is not immediately available, then within 2 to 3 business days, you will receive an estimated availability timeframe for your inquiry or order along with various delivery options. Repository strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping. We will note and try to accommodate requests for specific ages of Repository strains but cannot guarantee provision of these strains at specific ages. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, please let us know.

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1500 unique mouse models across a vast array of research areas. Breeding colonies provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. If a Repository strain is not immediately available, then within 2 to 3 business days, you will receive an estimated availability timeframe for your inquiry or order along with various delivery options. Repository strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping. We will note and try to accommodate requests for specific ages of Repository strains but cannot guarantee provision of these strains at specific ages. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, please let us know.

Control Information

  Control
   000664 C57BL/6J (approximate)
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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