Description

Strain Information

Type Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Mating System Heterozygote x C57BL/6J (000664)         (Female x Male)   21-JAN-13 Mating System C57BL/6J (000664) x Heterozygote         (Female x Male)   17-DEC-12 Species laboratory mouse Generation ?+pN1+N1 (11-MAR-13) Generation Definitions   Donating Investigator Bernardo Rudy,   NYU School of Medicine

Description
The transmembrane auxillary subunit, dipeptidylpeptidase 6 (Dpp6), is expressed in dendrites of CA1 pyramidal neurons and other areas of the brain. It is an auxiliary subunit of potassium channels containing Kv4 (Kcnd) pore forming subunits. DPP6 regulates the expression of Kv4.2 (Kcnd2) as well as the subcellular pattern of expression and properties of Kv4-containing A-type K⁺ channels. CA1 pyramidal neuron apical dendrites in mice homozygous for this null allele exhibit a loss of A-type K⁺ current in distal dendrites, an increased depolarizing shift in the inactivation curve of proximal dendrites, and a slower recovery from inactivation. These effects result in hyperexcitable dendrites with enhanced backpropagation of action potentials and long term potentiation. Mice that are homozygous for the targeted mutation are viable, fertile, normal in size. This mutant mouse strain may be useful in studies of dendritic function, potassium currents and their relation to behavior.

Development
A targeting vector was designed to insert a loxP site upstream of exon 2 followed by a frt-flanked neomycin resistance (neo) cassette, and a second loxP site downstream of exon 2 of the dipeptidylpeptidase 6 (Dpp6) gene. The construct was electroporated into C57BL/6-derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and the resulting chimeric mice were bred to C57BL/6 mice. Mice were crossed to a Cre deleter strain on a C57BL/6 background to remove exon 2 and the neo cassette. Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony.

Control Information

	Control
	Wild-type from the colony
	000664 C57BL/6J
Considerations for Choosing Controls

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. Ventricular Fibrillation, Paroxysmal Familial, 2; VF2   (DPP6)

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

Dpp6^tm1.1Dahn/Dpp6^tm1.1Dahn

        involves: C57BL/6

• nervous system phenotype
• abnormal afterhyperpolarization
  • enhanced due to slower A-current inactivation during repolarization   (MGI Ref ID J:178547)
• abnormal synaptic transmission
  • CA1 pyramidal neuron apical dendrites are hyperexcitable compared with wild-type neurons   (MGI Ref ID J:178547)
  • however, somatic membrane excitability and GABAergic currents are normal   (MGI Ref ID J:178547)
• • abnormal channel response
    • mice lack the distal dendritic A-type potassium current gradient compared with wild-type mice   (MGI Ref ID J:178547)
    • calcium electrogenesis is enhanced in CA1 dendrites compared to in wild-type cells   (MGI Ref ID J:178547)
    • remaining A-type potassium channels in dendrites are Kcna4 mediated   (MGI Ref ID J:178547)
  • abnormal long term potentiation
    • neurons exhibit extended spike-timing window for long term potentiation compared with wild-type neurons   (MGI Ref ID J:178547)

View Research Applications

Research Applications

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

Neurobiology Research
Channel and Transporter Defects
      potassium

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Dpp6tm1.1Dahn
Allele Name		targeted mutation 1.1, Dax A Hoffman
Allele Type		Targeted (knock-out)
Mutation Made By		Bernardo Rudy,   NYU School of Medicine
Strain of Origin		B6.Cg-Thy1
Gene Symbol and Name		Dpp6, dipeptidylpeptidase 6
Chromosome		5
Gene Common Name(s)		B930011P16Rik; DPP VI; DPPX; Dpp-6; Gm1377; In(5)6H-p; LOC384168; Peplb; RIKEN cDNA B930011P16 gene; Rw; VF2; gene model 1377, (NCBI); inversion, Chr 5, Harwell 6, proximal; peptidase-like brain protein;
Molecular Note		A loxP site was inserted upstream of exon 2. An FRT-flanked neo cassette with a 3' loxP site was inserted downstream of exon 2. Cre-mediated recombination removed exon 2 and the neo cassette. Immunohistochemistry confirmed the absence of protein expression in the brain. [MGI Ref ID J:178547]

Genotyping

Genotyping Information

Genotyping Protocols

Dpp6^tm1.1Dahnalternate1, Separated PCR
Dpp6^tm1.1Dahn, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Sun W; Maffie JK; Lin L; Petralia RS; Rudy B; Hoffman DA. 2011. DPP6 establishes the A-type K(+) current gradient critical for the regulation of dendritic excitability in CA1 hippocampal neurons. Neuron 71(6):1102-15. [PubMed: 21943606]  [MGI Ref ID J:178547]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           FGB29

Colony Maintenance

Breeding & Husbandry	While maintaining a live colony, these mice are bred as homozygotes.
Mating System	Heterozygote x C57BL/6J (000664)         (Female x Male)   21-JAN-13
	C57BL/6J (000664) x Heterozygote         (Female x Male)   17-DEC-12
Diet Information	LabDiet® 5K52/5K67

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

 

This strain is currently Under Development - Now Accepting Orders.
Estimated Available for Distribution Date: 22-JUL-13

Please note: You may now place orders for this strain although it is not yet ready for distribution. Estimated available for distribution dates are provided to keep customers better informed on strains under development. Please note that our Colony Managers routinely monitor the target date and edit it based on breeding performance and other factors. The length of time it takes to make a new strain available for distribution depends on genotype, age, number of animals sent by the Donating Investigator, breeding performance, additional strain development (backcrossing, making homozygous), and anticipated demand for the strain.

Control Information

	Control
	Wild-type from the colony
	000664 C57BL/6J
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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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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