Overview

Also Known As: Cdkl5^R59X

Cdkl5^R59X knock-in mice, carrying a nonsense mutation at arginine 59 of Cdkl5 and are useful when studying neurodevelopmental disorders including atypical Rett syndrome, autism spectrum disorders, and early infantile epileptic encephalopathy 2.

Donating Investigator

Zhaolan (Joe) Zhou, University of Pennsylvania

Genetic overview

Genetic Background	Generation

Cdkl5^tm2.1Joez

Allele Type	Gene Symbol	Gene Name
Targeted (Humanized sequence)	Cdkl5	cyclin-dependent kinase-like 5

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Research Applications

Cell Biology Research
Neurobiology Research
Developmental Biology Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

Cyclin-dependent kinase-like 5 (Cdkl5) is an X-linked gene encoding a serine/threonine kinase that is highly expressed in the brain. Genetic mutations that disrupt CDKL5 function have been found in humans with neurodevelopmental disorders including atypical Rett syndrome (RTT), autism spectrum disorders (ASDs), and early infantile epileptic encephalopathy 2 (EIEE2). These individuals, classified under CDKL5 Disorder for the common genetic defect, are characterized by early-onset seizures, intellectual disability, and autistic features.

Cdkl5^R59X knock-in mice, carrying a nonsense mutation at arginine 59 of Cdkl5, were developed to mimic exactly the same mutation found in patients with CDKL5 disorder. R59X leads to an early truncation at the N-terminal kinase domain of CDKL5, resulting in a loss-of-function. Male carriers show hyperactivity, motor impairments, and deficits in social interaction, learning and memory, with the absence of spontaneous seizures. Homozygous females and hemizygous males are viable but are poor breeders. When maintaining a live colony, heterozygous females may be bred to wildtype males.

Development

A targeting vector was designed to insert a frt-flanked neomycin resistance (neo) cassette downstream of exon 5, and a single nucleotide change of C to T, leading to a nonsense mutation at arginine 59 (R59X) of the Cyclin-dependent kinase-like 5 (Cdkl5) gene. The construct was electroporated into C57BL/6N embryonic stem (ES) cells. Correctly targeted ES cells were injected into BALB/c blastocysts and resulting chimeric mice were bred with B6.Cg-Tg(ACTFLPe)9205Dym/J (Stock No. 005703) to remove the neo cassette. Resulting offspring were bred to C57BL/6J mice (Stock No. 000664) for at least 10 generations to establish a colony of Cdkl5^R59X knock-in mice. Upon arrival at The Jackson Laboratory, oocytes were used to rederive a live colony.

Control Suggestions

Wild-type from the colony

Approximate Controls

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Tang S; Terzic B; Wang IJ; Sarmiento N; Sizov K; Cui Y; Takano H; Marsh ED; Zhou Z; Coulter DA. 2019. Altered NMDAR signaling underlies autistic-like features in mouse models of CDKL5 deficiency disorder. Nat Commun 10(1):2655PubMed: 31201320 MGI: J:276174

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Genetics

Cdkl5^tm2.1Joez

Allele Symbol: Cdkl5^tm2.1Joez

Allele Name	targeted mutation 2.1, Zhaolan Zhou
Allele Type	Targeted (Humanized sequence)
Allele Synonym(s)	targeted mutation 2.1, Zhaolan Zhou; Cdkl5^tm2.1Joez
Gene Symbol and Name	Cdkl5, cyclin-dependent kinase-like 5
Gene Synonym(s)	cDNA sequence BC038161; Stk9; STK9; EIEE2; ISSX; BC038161; serine/threonine kinase 9; Stk9; CFAP247
Strain of Origin	C57BL/6N
Chromosome	X
Molecular Note	A targeting vector was designed to insert a FRT-flanked neomycin resistance (neo) cassette downstream of exon 5, and a single nucleotide change of C to T, leading to a nonsense mutation at arginine 59 (R59X). Flp-mediated recombination removed the neo cassette.

Disease/Phenotype

Disease Terms

Research Areas By Genotype

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

Cell Biology Research
- Signal Transduction
Neurobiology Research
- Neurodevelopmental Defects
  - Autism
  - Rett's syndrome
Developmental Biology Research
- Neurodevelopmental Defects

Mammalian Phenotype Terms by Genotype

References

Tang S; Terzic B; Wang IJ; Sarmiento N; Sizov K; Cui Y; Takano H; Marsh ED; Zhou Z; Coulter DA. 2019. Altered NMDAR signaling underlies autistic-like features in mouse models of CDKL5 deficiency disorder. Nat Commun 10(1):2655PubMed: 31201320 MGI: J:276174

Additional - Cdkl5^tm2.1Joez related

Technical Support

Contact Technical Support

Genotyping Protocols
- Sanger sequencing: Cdkl5^tm2.1Joez Alternate1
- Genotyping resources and troubleshooting
Breeding Considerations

Homozygous females and hemizygous males are viable but are poor breeders. When maintaining a live colony, heterozygous females may be bred to wildtype males.
- Additional Breeding and Husbandry Support
Citation
When using the Cdkl5^R59X mouse strain in a publication, please cite the originating article(s) and include JAX stock #028856 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service	Genotype	Price
	Heterozygous females or wildtype males for Cdkl5<tm2.1Joez>

We will fulfill your order by providing at least two carriers for each strain ordered. The total number, sex, and genotypes provided will vary, although typically 8 or more animals are provided. Please check genotypes which will be recovered. While the genotypes of all animals produced will be communicated to you prior to scheduling shipment, the genotypes of animals provided may not reflect the mating scheme and genotypes described in the strain description. Animals are typically ready to ship in 11-14 weeks. If a second recovery is required to produce the minimum number of animals, then delivery time would increase to approximately 25 weeks. If we fail to produce animals of the correct genotype, you will not be charged. We 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.

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

The Jackson Laboratory's Genotype Promise

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.

Terms Of Use

Terms of Use

General Terms and Conditions

Questions about Terms of Use

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

JAX® Mice, Products & Services Conditions of Use

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Also Known As: Cdkl5R59X

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Approximate Controls

Additional Information

Selected References

Cdkl5tm2.1Joez

Allele Symbol: Cdkl5tm2.1Joez

Disease Terms

Research Areas By Genotype

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

Mammalian Phenotype Terms by Genotype

References

Additional - Cdkl5tm2.1Joez related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - Pricing

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms of Use

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Also Known As: Cdkl5^R59X

Cdkl5^tm2.1Joez

Allele Symbol: Cdkl5^tm2.1Joez

Additional - Cdkl5^tm2.1Joez related