Cdkl5 floxed mice contain loxP sites flanking exon 6 the X-linked cyclin-dependent kinase-like 5 (Cdkl5) gene, making them 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 floxed mice contain loxP sites flanking exon 6 of the X-linked cyclin-dependent kinase-like 5 (Cdkl5) gene. Cre Recombinase-dependent removal of murine exon 6, corresponding to exon 7 of human CDKL5, mimics a splice mutation found in humans that results in the skipping of exon 7, generating a premature stop codon and early truncation CDKL5 in its N-terminal kinase domain. For example, when bred to B6.FVB-Tg(EIIa-cre)C5379Lmgd/J mice (Stock No. 003724), male carriers, lacking CDKL5 expression, 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.
Of note, the knock-out version of this allele is available as Stock No. 021967.
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 129Sv-derived embryonic stem (ES) cells. Correctly targeted ES cells were transfected with a Cre-expressing plasmid and ES cell clones with selective Neo removal, leaving floxed exon 6, were injected into C57BL/6 blastocysts. Resulting chimeric mice were bred to C57BL/6J mice for germline transmission and were subsequently backcrossed to C57BL/6J mice for 10 generations to establish a colony of Cdkl5 floxed mice. Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation.
A 48 SNP (single nucleotide polymorphism) panel analysis, with 43 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. While the 43 markers throughout the genome suggested a C57BL/6 genetic background, 3 of 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a mixed C57BL/6J ; C57BL/6N genetic background.
|Allele Name||targeted mutation 1.2, Zhaolan Zhou|
|Allele Type||Targeted (Conditional ready (e.g. floxed), No functional change)|
|Gene Symbol and Name||Cdkl5, cyclin-dependent kinase-like 5|
|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, but not exon 6.|
When maintaining a live colony, homozygous females may be bred to hemizygous males. Mutation is X-linked.
When using the Cdkl5 floxed mouse strain in a publication, please cite the originating article(s) and include JAX stock #030523 in your Materials and Methods section.
"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCT(S)" means biological materials supplied by JACKSON, and their derivatives. "SERVICES" means projects conducted by JACKSON for other parties that may include but are not limited to the use of MICE or PRODUCTS. "RECIPIENT" means each recipient of MICE, PRODUCTS, or SERVICES provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than internal research, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services. Acceptance of MICE, PRODUCTS or SERVICES from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON’s prior written authorization.
MICE, PRODUCTS AND SERVICES ARE PROVIDED "AS IS". JACKSON EXTENDS NO WARRANTIES OF ANY KIND, EITHER EXPRESS, IMPLIED, OR STATUTORY, WITH RESPECT TO MICE, PRODUCTS OR SERVICES, INCLUDING ANY IMPLIED WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OR ANY WARRANTY OF NON-INFRINGEMENT OF ANY PATENT, TRADEMARK, OR OTHER INTELLECTUAL PROPERTY RIGHTS.
In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of, PRODUCTS or SERVICES, JACKSON will, at its option, provide credit or replacement for the PRODUCT received or the SERVICES provided; JACKSON makes no other representations and this shall be the exclusive remedy of the purchaser. Please note specific policy for live mice.
Consistent with the requirement for a written understanding regarding animal care and use, the JACKSON Animal Care and Use Committee will review the animal care and use protocol(s) associated with any SERVICES to be performed at JACKSON, and JACKSON shall have ultimate responsibility and authority for the care of animals while on site or in JACKSON custody.
In no event shall JACKSON, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, PRODUCTS, or SERVICES, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS, or SERVICES from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.
MICE, PRODUCTS or SERVICES are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.
The foregoing represents the General Terms and Conditions applicable to JACKSON’s MICE, PRODUCTS or SERVICES. In addition, special terms and conditions of sale of certain MICE, PRODUCTS, or SERVICES may be set forth separately in JACKSON web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, PRODUCTS and SERVICES by JACKSON, and by its licensees and distributors.
Acceptance of delivery of MICE, PRODUCTS or SERVICES shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on JACKSON, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, PRODUCTS or SERVICES by JACKSON.