Cdkl5R59X 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.
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.
Cdkl5R59X 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.
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 Cdkl5R59X knock-in mice. Upon arrival at The Jackson Laboratory, oocytes were used to rederive a live colony.
|Allele Name||targeted mutation 2.1, Zhaolan Zhou|
|Allele Type||Targeted (Humanized sequence)|
|Allele Synonym(s)||targeted mutation 2.1, Zhaolan Zhou; Cdkl5tm2.1Joez|
|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|
|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.|
Homozygous females and hemizygous males are viable but are poor breeders. When maintaining a live colony, heterozygous females may be bred to wildtype males.
When using the Cdkl5R59X mouse strain in a publication, please cite the originating article(s) and include JAX stock #028856 in your Materials and Methods section.
|Heterozygous females or wildtype males for Cdkl5<tm2.1Joez>|
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