Strain Name:

C57BL/6-Tg(Camk2a-ESR1/Disc1*)2698.1Sva/J

Stock Number:

008088

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Availability:

Repository- Live

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These DISC1-cc transgenic mice have expression of a tamoxifen-inducible, LBDG521R-DISC1-cc fusion protein directed to the branches of cortex, hippocampus, striatum, and cerebellum neurons (cytoplasm) of the forebrain by the mouse CaMKIIα promoter. These mice allow inducible and reversible expression of a dominant-negative isoform of disrupted-in-schizophrenia-1, and may be useful to study how interruption of DISC1 function at specific time points during brain development affects schizophrenia or other neurological disorders.

Description

Strain Information

Former Names C57BL/6-Tg(Camk2a-ESR1/Disc1)2698.1Sva/J    (Changed: 21-MAY-08 )
Type Transgenic;
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Mating SystemNoncarrier x Hemizygote         (Female x Male)   15-NOV-12
Mating SystemHemizygote x Noncarrier         (Female x Male)   15-NOV-12
Specieslaboratory mouse
GenerationN8pN1+F4 (04-AUG-14)
Generation Definitions
 
Donating Investigator Alcino J. Silva,   University of California, Los Angeles

Description
Mice hemizygous for this DISC1-cc transgene are viable and fertile, with expression of a tamoxifen-inducible, LBDG521R-DISC1-cc fusion protein directed to the branches of cortex, hippocampus, striatum, and cerebellum neurons (cytoplasm) of the forebrain by the mouse CaMKIIα promoter. The fusion protein consists of a truncated mutant isoform of the mouse disrupted-in-schizophrenia-1 gene (DISC1-cc; containing only residues (671-852) critical for NUDEL and Lis1 binding) and a mutant form of the human estrogen receptor ligand binding domain (LBDG521R; which is unable to bind its natural ligand, estrogen, at physiological concentrations but will bind the synthetic ligand, 4-hydroxytamoxifen). Prior to tamoxifen administration, the fusion protein is sequestered by chaperone proteins and is degraded. Upon tamoxifen binding, the fusion protein is released from the chaperone proteins and is then free to compete/interfere with endogenous Disc1 binding, thus having a dominant-negative function. Early postnatal, but not adult, tamoxifen-induced expression of the fusion protein results in a cluster of schizophrenia-related phenotypes, including reduced hippocampal dendritic complexity, depressive-like traits, abnormal spatial working memory, and reduced sociability. Of note, the homozygous phenotype is not yet characterized (July 2012) as the donating investigator has not attempted to breed hemizygous mice together to make homozygous mice.

Development
The DISC1-cc transgene was designed with a CaMKIIα promoter controlling an HA-tagged, LBDG521R-DISC1-cc fusion protein. Specifically, this transgene contains a mouse α-calmodulin kinase II promoter, hybrid intron in the 5' untranslated leader, HA virus-tag sequence, mutant form of the estrogen ligand biding domain (LBDG521R) cDNA fused 5' to a truncated mouse DISC1 cDNA (DISC1-cc; encoding the C-terminal protein residues 671-852), and polyA sequence. This transgene was injected into the pronuclei of C57BL/6 zygotes. The resulting chimeric founders (line 2698.1) were subsequently backcrossed to C57BL/6NTac mice for at least nine generations prior to sending to The Jackson Laboratory Repository in 2012. Upon arrival, transgenic mice were bred at least one generation to C57BL/6NJ inbred mice (Stock No. 005304) to establish The Jackson Laboratory Repository colony.

Control Information

  Control
   Noncarrier
   005304 C57BL/6NJ
 
  Considerations for Choosing Controls

Related Strains

View Strains carrying other alleles of Camk2a     (21 strains)

View Strains carrying other alleles of ESR1     (31 strains)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI
- Characteristics of this human disease are associated with transgenes and other mutation types in the mouse.
Schizophrenia; SCZD
- Potential model based on transgenic expression of an ortholog of a human gene that is associated with this disease. Phenotypic similarity to the human disease has not been tested.
Breast Cancer   (ESR1)
Estrogen Receptor 1; ESR1   (ESR1)
Estrogen Resistance; ESTRR   (ESR1)
Migraine with or without Aura, Susceptibility to, 1   (ESR1)
Myocardial Infarction, Susceptibility to   (ESR1)
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

Tg(Camk2a-ESR1/Disc1*)2698.1Sva/0

        involves: C57BL/6 * C57BL/6NTac
  • behavior/neurological phenotype
  • abnormal social investigation
    • in a social choice paradigm, adult mice treated with tamoxifen at P7 spend significantly more time in empty chamber away from stimulus mouse than in stimulus mouse chamber compared to controls   (MGI Ref ID J:127235)
    • with tamoxifen injection at adulthood (6 hours prior to testing), transgenic mice show no difference from adult controls   (MGI Ref ID J:127235)
    • social withdrawal   (MGI Ref ID J:127235)
  • abnormal spatial working memory
    • adult mice injected with tamoxifen at P7 show deficits in spatial working memory in a working memory test (delayed nonmatched to place task, DNMTP) compared to adult controls (wild-type and vehicle-treated transgenic animals)   (MGI Ref ID J:127235)
    • with tamoxifen injection at adulthood (6 hours prior to testing), transgenic mice show no difference from adult wild-type   (MGI Ref ID J:127235)
  • behavioral despair
    • in forced-swim test, adult mice treated with tamoxifen at P7 display depressive-like behavior as demonstrated by shorter latencies between floating episodes than those of control mice   (MGI Ref ID J:127235)
    • with tamoxifen injection at adulthood (6 hours prior to testing), transgenic mice show no difference from adult controls   (MGI Ref ID J:127235)
  • nervous system phenotype
  • abnormal CNS synaptic transmission
    • adult mice treated with tamoxifen at P7 show reduced hippocampal synaptic input/output function compared to controls   (MGI Ref ID J:127235)
    • paired pulse facilitation and long term potentiation in mice treated at P7 are both normal indicating that presynaptic function and LTP are unaffected by transgenic protein expression   (MGI Ref ID J:127235)
  • abnormal neuron morphology
    • reduced dendritic complexity in adult mice treated with tamoxifen at P7   (MGI Ref ID J:127235)
    • abnormal dendrite morphology
      • numbers of branch points and intersections in hippocampal neurons in adult mice treated with tamoxifen at P7 are reduced compared to controls;   (MGI Ref ID J:127235)
View Research Applications

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

Neurobiology Research
Behavioral and Learning Defects
Cortical Defects
Neurodevelopmental Defects

Research Tools
Neurobiology Research

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Tg(Camk2a-ESR1/Disc1*)2698.1Sva
Allele Name transgene insertion 2698.1, Alcino J Silva
Allele Type Transgenic (Inserted expressed sequence)
Common Name(s) DISC-cc; LBDG521R-DISC1-cc;
Mutation Made By Alcino Silva,   University of California, Los Angeles
Strain of OriginC57BL/6
Expressed Gene ESR1, estrogen receptor 1, human
Promoter Camk2a, calcium/calmodulin-dependent protein kinase II alpha, mouse, laboratory
Molecular Note The transgene construct is composed of a mouse a-calmodulin kinase II promoter, a hybrid intron in the 5' untranslated leader, a HA virus-tag sequence, and a mutant form of the estrogen ligand biding domain (LBDG521R) cDNA fused 5' to a truncated mouse DISC1 cDNA (DISC1-cc; encoding the C-terminal protein residues 671-852), and a polyA sequence. Upon tamoxifen induction of fusion gene expression, the LBDG521R-DISC1-cc fusion protein is directed to the cortex, hippocampus, striatum, and cerebellum by the CaMKIIa promoter. Immunohistochemical expression of mutant protein is observed in the forebrain in the branches and cytoplasm of neurons. [MGI Ref ID J:127235]
 
 

Genotyping

Genotyping Information

Genotyping Protocols

Tg(Camk2a-Creb1/Esr1)3Sva, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Additional References

Tg(Camk2a-ESR1/Disc1*)2698.1Sva related

Kvajo M; McKellar H; Gogos JA. 2012. Avoiding mouse traps in schizophrenia genetics: lessons and promises from current and emerging mouse models. Neuroscience 211:136-64. [PubMed: 21821099]  [MGI Ref ID J:184660]

Li W; Zhou Y; Jentsch JD; Brown RA; Tian X; Ehninger D; Hennah W; Peltonen L; Lonnqvist J; Huttunen MO; Kaprio J; Trachtenberg JT; Silva AJ; Cannon TD. 2007. Specific developmental disruption of disrupted-in-schizophrenia-1 function results in schizophrenia-related phenotypes in mice. Proc Natl Acad Sci U S A 104(46):18280-5. [PubMed: 17984054]  [MGI Ref ID J:127235]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           FGB27

Colony Maintenance

Breeding & HusbandryWhen maintaining a live colony, hemizygotes are bred to wildtype (noncarrier) mice from the colony or to C57BL/6NJ inbred mice (Stock No. 005304). The donating investigator has not attempted to breed hemizygous mice together to make homozygous for the transgene (July 2012).
Mating SystemNoncarrier x Hemizygote         (Female x Male)   15-NOV-12
Hemizygote x Noncarrier         (Female x Male)   15-NOV-12
Diet Information LabDiet® 5K52/5K67

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 MaleHemizygous for Tg(Camk2a-ESR1/Disc1*)2698.1Sva  
Price per Pair (US dollars $)Pair Genotype
$304.00Hemizygous for Tg(Camk2a-ESR1/Disc1*)2698.1Sva x Noncarrier  
$304.00Noncarrier x Hemizygous for Tg(Camk2a-ESR1/Disc1*)2698.1Sva  

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

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 MaleHemizygous for Tg(Camk2a-ESR1/Disc1*)2698.1Sva  
Price per Pair (US dollars $)Pair Genotype
$395.20Hemizygous for Tg(Camk2a-ESR1/Disc1*)2698.1Sva x Noncarrier  
$395.20Noncarrier x Hemizygous for Tg(Camk2a-ESR1/Disc1*)2698.1Sva  

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

Control Information

  Control
   Noncarrier
   005304 C57BL/6NJ
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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