Overview

Also Known As: Cdkl5 KO

Cdkl5 knockout mice exhibit autistic-like behavioral abnormalities, deficits in neural circuit communication, and alterations in multiple signal transduction pathways. They may be useful when studying neurodevelopmental disorders such as Rett syndrome, autism spectrum disorders, and early infantile epileptic encephalopathy.

Donating Investigator

Zhaolan (Joe) Zhou, University of Pennsylvania

Genetic overview

Genetic Background	Generation
	?+pN1F11 (2019-03-19 00:00:00)

Cdkl5^tm1.1Joez

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Cdkl5	cyclin-dependent kinase-like 5

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Research Applications

Neurobiology Research
Developmental Biology Research

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Base Price

Starting at:

$0.00 Domestic price for male 4-week

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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 knockout mice, lacking exon 6 of Cdkl5 (corresponding to exon 7 of human CDKL5), were developed to mimic a splice mutation found in humans that results in the skipping of exon 7, generating a premature stop codon and really truncation CDKL5 in its N-terminal kinase domain. Male carriers show autistic-like behavioral abnormalities, hyperactivity, motor impairments, decreased anxiety, deficits in social interaction, and impaired learning and memory with absence of spontaneous seizures. They also exhibit deficits in neural circuit communication. Cdkl5 knockout males have alterations in phosphorylation profiles in forebrain regions including the striatum, somatosensory cortex, and hippocampus where CDKL5 is expressed. Multiple signal transduction pathways, including AKT-mTOR cascade, are disrupted in Cdkl5 knockout mice. Mice that are homozygous for this allele are viable and fertile.

Of note, the floxed version of this allele is available as Stock No. 030523.

Development

A targeting vector was designed to insert a loxP-flanked neomycin resistance (neo) cassette upstream of exon 6, and a single loxP site downstream of exon 6 of the X-linked cyclin-dependent kinase-like 5 (Cdkl5) gene. The construct was electroporated into 129 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts and resulting chimeric mice were bred with B6.FVB-Tg(EIIa-cre)C5379Lmgd/J mice (Stock No. 003724) to remove the neo cassette and exon 6. Resulting offspring were bred to C57BL/6J mice for at least 10 generations to establish a colony of Cdkl5 knockout mice. Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation.

Control Suggestions

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Wang IT; Allen M; Goffin D; Zhu X; Fairless AH; Brodkin ES; Siegel SJ; Marsh ED; Blendy JA; Zhou Z. 2012. Loss of CDKL5 disrupts kinome profile and event-related potentials leading to autistic-like phenotypes in mice. Proc Natl Acad Sci U S A 109(52):21516-21PubMed: 23236174 MGI: J:193172

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Genetics

Cdkl5^tm1.1Joez

Allele Symbol: Cdkl5^tm1.1Joez

Allele Name	targeted mutation 1.1, Zhaolan Zhou
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	Cdkl5^tm1.1Joez; targeted mutation 1.1, Zhaolan Zhou
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	129
Chromosome	X
Molecular Note	A floxed neo cassette was inserted upstream of exon 6. A loxP site was inserted downstream of exon 6. Cre-mediated recombination removed the neo cassette and exon 6. Western blot analysis confirmed the absence of protein expression.

Disease/Phenotype

Disease Terms

Research Areas By Genotype

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

Neurobiology Research
- Neurodevelopmental Defects
  - Autism
  - Rett's syndrome
- Ataxia (Movement) Defects
- Behavioral and Learning Defects
Developmental Biology Research
- Neurodevelopmental Defects

Mammalian Phenotype Terms by Genotype

The following phenotype relates to a compound genotype created using this strain

Genotype: Cdkl5^tm1.1Joez/Y
B6.129(FVB)-Cdkl5

behavior/neurological phenotype

abnormal nest building behavior
- impaired nesting

decreased anxiety-related response
- in a zero maze test

hyperactivity

impaired contextual conditioning behavior

impaired coordination

impaired cued conditioning behavior

limb grasping
- fore and hind limb

social withdrawal
- impaired social interaction

nervous system phenotype

abnormal nervous system electrophysiology
- mice exhibit deficits in auditory-evoked event-related potentials with aberrant waveform compared with wild-type mice
- mice exhibit disruptions in low-frequency event-related neuronal oscillations compared with wild-type mice

mammalian phenotype

nervous system phenotype
- Normal - mice exhibit normal EEG patterns and no spontaneous seizures

taste/olfaction phenotype
- Normal - mice exhibit normal olfaction

References

Wang IT; Allen M; Goffin D; Zhu X; Fairless AH; Brodkin ES; Siegel SJ; Marsh ED; Blendy JA; Zhou Z. 2012. Loss of CDKL5 disrupts kinome profile and event-related potentials leading to autistic-like phenotypes in mice. Proc Natl Acad Sci U S A 109(52):21516-21PubMed: 23236174 MGI: J:193172

Additional References

Lee KZ; Liao W. 2018. Loss of CDKL5 disrupts respiratory function in mice. Respir Physiol Neurobiol 248:48-54PubMed: 29208534 MGI: J:271843

Additional - Cdkl5^tm1.1Joez related

Technical Support

Contact Technical Support

Genotyping Protocols
- Standard PCR:Cdkl5^tm1.1Joez
- Genotyping resources and troubleshooting
Dietary Information
- LabDiet® 5K52 formulation (6% fat)
Breeding Considerations

When maintaining a live colony, homozygous females may be bred to hemizygous males. Mutation is X-linked.
- Additional Breeding and Husbandry Support
Mating System
- Homozygote x Hemizygote
Citation
When using the Cdkl5 KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #021967 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

AX10 (Standard)

Pricing & Availability

Please Inquire

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service	Genotype	Price
	X linked females are Heterozygous or wild type and males wildtype for Cdkl5<tm1.1Joez>

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.

Related Products and Services

Frozen Mouse Embryo	B6.129(FVB)-Cdkl5<tm1.1Joez>/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	B6.129(FVB)-Cdkl5<tm1.1Joez>/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	B6.129(FVB)-Cdkl5<tm1.1Joez>/J Frozen Embryo	$3373.50
Frozen Mouse Embryo	B6.129(FVB)-Cdkl5<tm1.1Joez>/J Frozen Embryo	$3373.50

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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.

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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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Licensing Information

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Also Known As: Cdkl5 KO

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Cdkl5tm1.1Joez

Allele Symbol: Cdkl5tm1.1Joez

Disease Terms

Research Areas By Genotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Cdkl5tm1.1Joez/YB6.129(FVB)-Cdkl5

behavior/neurological phenotype

nervous system phenotype

mammalian phenotype

References

Additional References

Additional - Cdkl5tm1.1Joez related

Genotyping Protocols

Dietary Information

Breeding Considerations

Mating System

Citation

Animal Health Reports

Live Mouse

Cryorecovery - Pricing

Related Products and Services

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

Cdkl5^tm1.1Joez

Allele Symbol: Cdkl5^tm1.1Joez

Genotype: Cdkl5^tm1.1Joez/Y
B6.129(FVB)-Cdkl5

Additional - Cdkl5^tm1.1Joez related