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Type Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse Generation ?+N1p (27-MAR-05)
Generation DefinitionsDonating Investigator Dr. Richard Palmiter, University of Washington Description
Mice that are homozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. No gene product (protein) is detected in brain homogenates by Western blot analysis. Beta-galactosidase activity pattern in homozygotes mimics endogenous gene expression. Total zinc levels in the hippocampus and cortex is reduced by approximately 20%. Histochemically reactive and immunoreactive synaptic vesicle zinc is undetectable. There is no N-(6-Methoxy-8-quinolyl)-p-Toluene-Sulfonamide (TSQ) fluorescence in hippocampal tissues, although it is detected in testis and pancreas. This mutant mouse strain may be useful in studies of zinc transport into synaptic vesicles.Development
A targeting vector containing neomycin resistance, beta-galactosidase and herpes simplex virus thymidine kinase genes was used to disrupt exons 1 through 4. The construct was electroporated into 129S4/SvJaeSor derived AK18.1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts.
| Control | ||
|---|---|---|
| See control note: | Wildtype mice from the colony or B6129SF2 mice (Stock No. 101045) may be used as controls. The B6129SF2 mice only provide an approximate genetic match to this B6;129 background. | |
| Considerations for Choosing Controls | ||
lacZ Expression Strains
View lacZ Expression Strains (255 strains)
Strains carrying other alleles of lacZ
View Strains carrying other alleles of lacZ (267 strains)
Fluorescent Proteins/lacZ Systems
View Mammalian Phenotype Terms
Mammalian Phenotype Terms provided by MGI
assigned by genotype
Slc30a3tm1Rpa/Slc30a3+
involves: 129S7/SvEvBrd * C57BL/6
- homeostasis/metabolism phenotype
- decreased brain zinc level
- heterozygotes display a ~10% reduction in total zinc levels in the hippocampus and cortex relative to wild-type mice (MGI Ref ID J:53059)
- Timm stain is reduced in the hippocampus, neocortex, piriform cortex, amygdala, entorhinal cortex, striatum, olfactory bulb, and cochlear nucleus of heterozygous mutant mice (MGI Ref ID J:53059)
- in the hippocampus, Timm staining is reduced in the mossy fibers projecting from dentate granule neurons to the hilus and s lucidum and s oriens of the CA3 region, and in projections to s radiatum and s oriens of the CA1 region (MGI Ref ID J:53059)
- Timm-staining is reduced within the synaptic vesicles of heterozygous mutant mossy fiber boutons (MGI Ref ID J:53059)
- TSQ fluorescenceis reduced by 47% in the hilus, 39% in the CA3 region, and 50% in the CA1 region of heterozygous mutant hippocampi (MGI Ref ID J:53059)
Slc30a3tm1Rpa/Slc30a3tm1Rpa
involves: 129S7/SvEvBrd * C57BL/6
- nervous system phenotype
- abnormal hippocampal mossy fiber morphology
- mutant hippocampi display normal mossy fiber bouton ultrastructure, with densely packed clear, round synaptic vesicles, a few dense core vesicles, and numerous mitochondria, but lack histochemically reactive zinc within the synaptic vesicles (MGI Ref ID J:53059)
- abnormal synaptic vesicle morphology
- no Timm-staining is observed within synaptic vesicles of homozygous mutant mossy fiber boutons, indicating that histochemically reactive zinc is eliminated from synaptic vesicles (MGI Ref ID J:53059)
- homeostasis/metabolism phenotype
- abnormal zinc homeostasis
- homozygotes exhibit impaired zinc transport into synaptic vesicles (MGI Ref ID J:53059)
- decreased brain zinc level
- homozygotes display a ~20% reduction in total zinc levels in the hippocampus and cortex relative to wild-type mice (MGI Ref ID J:53059)
- Timm stain (a stain for histochemically reactive zinc) is undetectable in the hippocampus, neocortex, piriform cortex, amygdala, entorhinal cortex, striatum, olfactory bulb, and cochlear nucleus of homozygous mutant mice (MGI Ref ID J:53059)
- in the hippocampus, Timm staining is undetectable in the mossy fibers projecting from dentate granule neurons to the hilus and s lucidum and s oriens of the CA3 region, and in projections to s radiatum and s oriens of the CA1 region (MGI Ref ID J:53059)
- no Timm-staining is observed within synaptic vesicles of homozygous mutant mossy fiber boutons (MGI Ref ID J:53059)
- in contrast, Timm staining is readily detectable in the choroid plexus and in convoluted tubule cells of the submaxillary gland, while TSQ fluorescence is still abundant in differentiating spermatids and in beta-islet cells of the pancreas (MGI Ref ID J:53059)
- TSQ fluorescence (a specific indicator of vesicular zinc) is undetectable in the hilus and CA3 and CA1 regions of mutant hippocampus (MGI Ref ID J:53059)
The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.
Slc30a3tm1Rpa/Slc30a3tm1Rpa
involves: 129S7/SvEvBrd * C57BL/6 * SJLView Research Applications
Research Applications
This mouse can be used to support research in many areas including:
Neurobiology Research
lacZ expression in neural tissue
Metabolic Defects
Neurotransmitter Receptor and Synaptic Vesicle Defects
Research Tools
lacZ Expression
Neurobiology Research
cell marker
| Allele Symbol | Slc30a3tm1Rpa | ||
|---|---|---|---|
| Allele Name | targeted mutation 1, Richard D Palmiter | ||
| Allele Type | Targeted (Reporter) | ||
| Common Name(s) | ZnT3; Znt3-; | ||
| Mutation Made By | Dr. Richard Palmiter, University of Washington | ||
| Strain of Origin | 129S7/SvEvBrd-Hprt<+> | ||
| ES Cell Line Name | AB1 | ||
| ES Cell Line Strain | 129S7/SvEvBrd-Hprt<+> | ||
| Site of Expression | lacZ replaces/mimics endogenous gene expression | ||
| Expressed Gene | lacZ, beta-galactosidase, E. coli | ||
| Molecular Note | Exons 1 through 4 were replaced with a cassette containing nuclear lacZ and neo. Encoded protein was undetectable in brain homogenates from homozygous mutant mice via Western blot analysis. Beta-galactosidase expression was used to observe the activity of the endogenous promoter. [MGI Ref ID J:53059] | ||
| Gene Symbol and Name | Slc30a3, solute carrier family 30 (zinc transporter), member 3 | ||
| Chromosome | 5 | ||
| Gene Common Name(s) | ZNT3; Znt3; zinc transporter 3; | ||
Genotyping Protocols
Slc30a3tm1Rpa, Standard PCR
Helpful Links
Genotyping resources and troubleshooting
Cole TB; Wenzel HJ; Kafer KE; Schwartzkroin PA; Palmiter RD. 1999. Elimination of zinc from synaptic vesicles in the intact mouse brain by disruption of the ZnT3 gene. Proc Natl Acad Sci U S A 96(4):1716-21. [PubMed: 9990090] [MGI Ref ID J:53059]
Slc30a3tm1Rpa relatedAdlard PA; Parncutt JM; Finkelstein DI; Bush AI. 2010. Cognitive loss in zinc transporter-3 knock-out mice: a phenocopy for the synaptic and memory deficits of Alzheimer's disease? J Neurosci 30(5):1631-6. [PubMed: 20130173] [MGI Ref ID J:157934]
Cole TB; Martyanova A; Palmiter RD. 2001. Removing zinc from synaptic vesicles does not impair spatial learning, memory, or sensorimotor functions in the mouse. Brain Res 891(1-2):253-65. [PubMed: 11164830] [MGI Ref ID J:107877]
Cole TB; Robbins CA; Wenzel HJ; Schwartzkroin PA; Palmiter RD. 2000. Seizures and neuronal damage in mice lacking vesicular zinc Epilepsy Res 39(2):153-69. [PubMed: 10759303] [MGI Ref ID J:62384]
Doering P; Danscher G; Larsen A; Bruhn M; Sondergaard C; Stoltenberg M. 2007. Changes in the vesicular zinc pattern following traumatic brain injury. Neuroscience 150(1):93-103. [PubMed: 17996379] [MGI Ref ID J:130773]
Doering P; Stoltenberg M; Penkowa M; Rungby J; Larsen A; Danscher G. 2010. Chemical blocking of zinc ions in CNS increases neuronal damage following traumatic brain injury (TBI) in mice. PLoS One 5(4):e10131. [PubMed: 20396380] [MGI Ref ID J:160158]
Friedlich AL; Lee JY; van Groen T; Cherny RA; Volitakis I; Cole TB; Palmiter RD; Koh JY; Bush AI. 2004. Neuronal zinc exchange with the blood vessel wall promotes cerebral amyloid angiopathy in an animal model of Alzheimer's disease. J Neurosci 24(13):3453-9. [PubMed: 15056725] [MGI Ref ID J:129255]
Lee JY; Cole TB; Palmiter RD; Koh JY. 2000. Accumulation of zinc in degenerating hippocampal neurons of ZnT3-null mice after seizures: evidence against synaptic vesicle origin J Neurosci (Online) 20(11):RC79. [PubMed: 10807937] [MGI Ref ID J:62436]
Lee JY; Cole TB; Palmiter RD; Suh SW; Koh JY. 2002. Contribution by synaptic zinc to the gender-disparate plaque formation in human Swedish mutant APP transgenic mice. Proc Natl Acad Sci U S A 99(11):7705-10. [PubMed: 12032347] [MGI Ref ID J:76863]
Lee JY; Kim JH; Palmiter RD; Koh JY. 2003. Zinc released from metallothionein-iii may contribute to hippocampal CA1 and thalamic neuronal death following acute brain injury. Exp Neurol 184(1):337-47. [PubMed: 14637104] [MGI Ref ID J:86693]
Linkous DH; Flinn JM; Koh JY; Lanzirotti A; Bertsch PM; Jones BF; Giblin LJ; Frederickson CJ. 2008. Evidence that the ZNT3 protein controls the total amount of elemental zinc in synaptic vesicles. J Histochem Cytochem 56(1):3-6. [PubMed: 17712179] [MGI Ref ID J:132521]
Lopantsev V; Wenzel HJ; Cole TB; Palmiter RD; Schwartzkroin PA. 2003. Lack of vesicular zinc in mossy fibers does not affect synaptic excitability of CA3 pyramidal cells in zinc transporter 3 knockout mice. Neuroscience 116(1):237-48. [PubMed: 12535956] [MGI Ref ID J:109296]
Martel G; Hevi C; Friebely O; Baybutt T; Shumyatsky GP. 2010. Zinc transporter 3 is involved in learned fear and extinction, but not in innate fear. Learn Mem 17(11):582-90. [PubMed: 21036893] [MGI Ref ID J:185894]
Martel G; Hevi C; Kane-Goldsmith N; Shumyatsky GP. 2011. Zinc transporter ZnT3 is involved in memory dependent on the hippocampus and perirhinal cortex. Behav Brain Res 223(1):233-8. [PubMed: 21545813] [MGI Ref ID J:177004]
Ponnoth DS; Nayeem MA; Kunduri SS; Tilley SL; Zeldin DC; Ledent C; Mustafa SJ. 2011. Role of omega-hydroxylase in adenosine-mediated aortic response through MAP kinase using A2A receptor knockout mice. Am J Physiol Regul Integr Comp Physiol :. [PubMed: 22160543] [MGI Ref ID J:178907]
Qian J; Noebels JL. 2006. Exocytosis of vesicular zinc reveals persistent depression of neurotransmitter release during metabotropic glutamate receptor long-term depression at the hippocampal CA3-CA1 synapse. J Neurosci 26(22):6089-95. [PubMed: 16738253] [MGI Ref ID J:109118]
Sindreu C; Palmiter RD; Storm DR. 2011. From the Cover: Zinc transporter ZnT-3 regulates presynaptic Erk1/2 signaling and hippocampus-dependent memory. Proc Natl Acad Sci U S A 108(8):3366-70. [PubMed: 21245308] [MGI Ref ID J:169120]
Animal Health Reports
Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.Colony Maintenance
Breeding & Husbandry The resulting chimeric animals were crossed to 129S4/SvJaeSor mice, and then backcrossed to C57BL/6 for 3 generations (June 2003).
| Pricing for USA, Canada and Mexico shipping destinations |
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Cryopreserved Mice - Ready for Recovery
Animals Provided
Price (US dollars $) Cryorecovery* $2250.00 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 |
|
Cryopreserved Mice - Ready for Recovery
Animals Provided
Price (US dollars $) Cryorecovery* $2925.00 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).
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Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
| Control | ||
|---|---|---|
| See control note: | Wildtype mice from the colony or B6129SF2 mice (Stock No. 101045) may be used as controls. The B6129SF2 mice only provide an approximate genetic match to this B6;129 background. | |
| Considerations for Choosing Controls | ||
| Control Pricing Information for Genetically Engineered Mutant Strains. | ||
For Licensing and Use Restrictions view the link(s) below:
- Use of MICE by companies or for-profit entities requires a license prior to shipping.
| phone: | 207-288-6470 |
| fax: | 207-288-6655 |
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