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.
Zhaolan (Joe) Zhou, University of Pennsylvania
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.
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.
|Allele Name||targeted mutation 1.1, Zhaolan Zhou|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||Cdkl5tm1.1Joez; 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|
|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.|
When maintaining a live colony, homozygous females may be bred to hemizygous males. Mutation is X-linked.
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.
|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.
|Frozen Mouse Embryo||$2,595.00 per straw or vial|
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