This targeted mutation of the potassium voltage-gated channel, shaker-related subfamily, member 2 (Kcna2) gene exhibits spontaneous seizures may be useful in studies of voltage dependent potassium channels and epilepsy.
Dr. Bruce L. Tempel, Univ of Washington School of Medicine
Homozygous mice appear normal at birth, however, by day 15 mice are smaller and exhibit explosive running and bouncing seizures sometimes followed by tonic extension accompanied by a shortness of breath (apnea). These seizures occur at a rate of less than one per day and have a 50% fatality rate. Mean lifespan is approximately 17 days on both the mixed C57BL/6-129S7 background and the C3H background. In homozygous mice, auditory neurons of the medial nucleus of the trapezoid body (MNTB) exhibit a decrease in action potential firing (hypoexcitable) and higher threshold current amplitude than wild-type mice. MNTB neurons in heterozygous mice exhibit an intermediate phenotype. The counter-intuitive decrease in activity with the deletion of Kv1.2 subunits occurs because replacement subunits (most likely Kv1.1) are lower-threshold than Kv1.2. This mutant mouse strain may be useful in studies of voltage dependent potassium channels and epilepsy.
In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.
A targeting vector containing the neomycin resistance gene was used to replace the open reading frame of the targeted gene. The construct was electroporated into 129S7/SvEvTac derived AB1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. The resulting chimeric animals were crossed to C3HeB/FeJ and backcrossed for greater than 30 generations. In 2008, as a result of breeding difficulties, the strain was backcrossed to CBA/CaJ for 2 generations. Upon arrival, mice were bred to C3HeB/FeJ for at least 1 generation to establish the colony.
|Allele Name||targeted mutation 1, Bruce L Tempel|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Kcna2, potassium voltage-gated channel, shaker-related subfamily, member 2|
|Strain of Origin||129S7/SvEvBrd-Hprt+|
|Molecular Note||A neomycin resistance cassette replaced the entire open reading frame. mRNAQ cannot be found by quantitative PCR and protein product cannot be identified by Western blot in extracts from homozygous mutant mice.|
|Mutations Made By|| |
Dr. Bruce Tempel, Univ of Washington School of Medicine
While maintaining a live colony, these mice are bred as heteroygotes. Mice homozygous for the mutation die by 17 days of age.
When using the STOCK Kcna2tm1Tem/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #010744 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.