Strain Name:

C57BL/6-Tg(Camk2a-AIDPak)21Stl/J

Stock Number:

013760

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dnPAK transgenic mice have a mouse Camk2a promoter directing postnatal forebrain expression of the mouse dominant negative autoinhibitory domain (AID) of the p21 protein (Cdc42/Rac)-activated kinase (Pak) gene. These mice may be useful for studying the causes of mental retardation, fragile X syndrome, autism, the regulation of synaptic structure and strength, and dendritic spine morphogenesis.

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

Former Names C57BL/6-Tg(Camk2a-AIDPAK)21Stl/J    (Changed: 26-OCT-10 )
Type Coisogenic; Mutant Strain; Transgenic;
Additional information on Genetically Engineered and Mutant Mice.
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Specieslaboratory mouse
GenerationF?pN1
Generation Definitions
 
Donating InvestigatorDr. Susumu Tonegawa,   Massachusetts Institute of Technology

Description
dnPAK transgenic mice have a mouse calcium/calmodulin-dependent protein kinase II alpha (Camk2a) promoter directing postnatal forebrain expression of the mouse dominant negative (dn) autoinhibitory domain (AID) of p21 protein (Cdc42/Rac)-activated kinase (Pak) gene (dnPAK). The AID is conserved in all three Pak genes (Pak1, Pak2, Pak3). Homozygous dnPAK mice are viable, fertile, and normal in size. Pak genes are expressed in multiple brain regions, including the cortex and hippocampus, and are critical regulators of actin remodeling. The activation of PAK catalytic activity requires the release of the catalytic domain from the AID and autophosphorylation of a gene specific threonine residue. dnPAK binds to the catalytic domain of PAK and blocks autophosphorylation, inhibiting activation of catalytic activity. dnPAK overexpression causes a decrease in the number of and increase is the size of cortical neuron dendritic spines. Also observed is an increase in the proportion of larger synapses. These cortical neurons exhibit impaired bidirectional modifiability of synaptic strength with enhanced long-term potentiation (LTP) and reduced long-term depression (LTD), leading to a deficit in consolidation and retention of spacial memory. These mice may be useful for studying the regulation of synaptic structure and strength, and dendritic spine morphogenesis associated with the causes of mental retardation, fragile X syndrome, and autism.

Development
The dnPAK transgene was designed with the mouse autoinhibitory domain (AID) of the p21 protein (Cdc42/Rac)-activated kinase (Pak) gene driven by a mouse calcium/calmodulin-dependent protein kinase II alpha (Camk2a) promoter, followed by a simian virus 40 (SV40) polyadenylation site. The transgene was microinjected into fertilized C57BL/6 oocytes and mice from founder line 21 were bred to C57BL/6 mice. Upon arrival at The Jackson Laboratory, transgenic mice were bred to C57BL/6J inbred mice (Stock No. 000664) to establish the colony.

Control Information

  Control
   Noncarrier
   000664 C57BL/6J
 
  Considerations for Choosing Controls

Related Strains

View Strains carrying other alleles of Camk2a     (22 strains)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI
- Potential model based on transgenic expression of a human gene that is associated with this disease. Phenotypic similarity to the human disease has not been tested.
Mental Retardation, X-Linked 30; MRX30   (PAK3)
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

Tg(Camk2a-AIDPak)21Stl/0

        C57BL/6-Tg(Camk2a-AIDPak)21Stl
  • nervous system phenotype
  • *normal* nervous system phenotype
    • the ratio of NMDAR to AMPAR mediated synaptic currents is normal   (MGI Ref ID J:90763)
    • abnormal dendritic spine morphology
      • the density of dendritic spines is lower in layer II/III of the temporal cortex compared to in wild-type mice   (MGI Ref ID J:90763)
      • cortical neurons exhibit shorter spine length compared with wild-type neurons   (MGI Ref ID J:90763)
      • however, dendritic length and number of branch point are normal and hippocampal CA1 pyramidal neurons exhibit normal dendritic spine density, dendritic length, and branch point numbers are normal   (MGI Ref ID J:90763)
    • abnormal miniature excitatory postsynaptic currents
      • the mean amplitude of AMPAR-mediated miniature excitatory postsynaptic currents (mEPSCs) is greater than in wild-type mice   (MGI Ref ID J:90763)
      • however, the mean frequency of AMPAR-mediated mEPSCs is normal   (MGI Ref ID J:90763)
    • abnormal synapse morphology
      • mice exhibit an increase in the proportion of larger synapses compared with wild-type mice   (MGI Ref ID J:90763)
      • abnormal synaptic vesicle number
        • the number of docked vesicles per bouton is greater than in wild-type neurons   (MGI Ref ID J:90763)
        • however, the density of docked vesicles is normal   (MGI Ref ID J:90763)
    • enhanced long term potentiation   (MGI Ref ID J:90763)
    • reduced long term depression   (MGI Ref ID J:90763)
  • behavior/neurological phenotype
  • abnormal long term spatial reference memory
    • in a hidden-platform Morris water maze 21 days after training, mice exhibit impaired consolidation/retention of spatial memory compared with wild-type mice   (MGI Ref ID J:90763)
    • however, acquisition of spatial memory is normal   (MGI Ref ID J:90763)
  • impaired contextual conditioning behavior
    • 24 hours after training   (MGI Ref ID J:90763)
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
Fragile X Mental Retardation Syndrome
Neurodevelopmental Defects
      Autism
Neurotransmitter Receptor and Synaptic Vesicle Defects
Receptor Defects

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Tg(Camk2a-AIDPak)21Stl
Allele Name transgene insertion 21, Susumu Tonegawa
Allele Type Transgenic (Inserted expressed sequence)
Common Name(s) dnPAK;
Strain of OriginC57BL/6
Expressed Gene Pak3, p21 protein (Cdc42/Rac)-activated kinase 3, mouse, laboratory
Promoter Camk2a, calcium/calmodulin-dependent protein kinase II alpha, mouse, laboratory
Molecular Note The dnPAK transgene was designed with the mouse autoinhibitory domain (AID) of the p21 protein (Cdc42/Rac)-activated kinase 3 (Pak3) gene tagged with myc and driven by a mouse calcium/calmodulin-dependent protein kinase II alpha (Camk2a) promoter, followed by a simian virus 40 (SV40) polyadenylation site. This domain is conserved in all three Pak genes (Pak1, Pak2, Pak3). Lines 21 and 110 were generated. [MGI Ref ID J:90763]
 
 

Genotyping

Genotyping Information

Genotyping Protocols

Tg(Camk2a-AIDPak)21Stl, Separated PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Hayashi ML; Choi SY; Rao BS; Jung HY; Lee HK; Zhang D; Chattarji S; Kirkwood A; Tonegawa S. 2004. Altered cortical synaptic morphology and impaired memory consolidation in forebrain- specific dominant-negative PAK transgenic mice. Neuron 42(5):773-87. [PubMed: 15182717]  [MGI Ref ID J:90763]

Additional References

Tg(Camk2a-AIDPak)21Stl related

Arsenault D; Dal-Pan A; Tremblay C; Bennett DA; Guitton MJ; De Koninck Y; Tonegawa S; Calon F. 2013. PAK inactivation impairs social recognition in 3xTg-AD Mice without increasing brain deposition of tau and Abeta. J Neurosci 33(26):10729-40. [PubMed: 23804095]  [MGI Ref ID J:199637]

Hayashi ML; Rao BS; Seo JS; Choi HS; Dolan BM; Choi SY; Chattarji S; Tonegawa S. 2007. Inhibition of p21-activated kinase rescues symptoms of fragile X syndrome in mice. Proc Natl Acad Sci U S A 104(27):11489-11494. [PubMed: 17592139]  [MGI Ref ID J:122818]

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 maintaining a live colony, homozygous mice may be bred.

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* $2140.00
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 10 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* $2782.00
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 10 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
   Noncarrier
   000664 C57BL/6J
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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