This strain has a targeted point reversion in Cdh23 that creates a predominantly C57BL/6N strain without the age-related hearing loss that is normally found in that inbred strain.
Kenneth Johnson, JAX
C57BL/6NJ mice develop age-related hearing loss due in large part to the Cdh23ahl allele, which is an A to G point mutation at c.753. Using homologous recombination in C57BL/6N-derived ES cells this point mutation was reverted to the wild-type sequence, and auditory brainstem response thresholds were normal at 16 kHz and 32 kHz throughout the 18 months assessed, but low frequency hearing loss, detected at 8kHz, still occurs. Homozygotes have only a very mild loss of outer hair cells at 18 months, whereas C57BL/6NJ mice have progressive and severe loss of outer and inner hair cells, with outer hair cell loss being more severe, and the damage is more severe in the base than the apex of the cochlea. Genotyping assay details for distinguishing the targeted 753G SNV allele from non-engineered alleles can be found in Johnson et al., 2017, Sci Rep 7:44450.
The sequence of Chromosome 10 from 60,527,162 bp through 60,536,889 bp (GRCm38), which contains the functional c.753G variant of Cdh23, was cloned from a 129S1-derived BAC, loxP-flanked PGK-Neo cassette was then inserted 178 bp downstream of the c.753G nucleotide, and homology arms were added to correctly target this sequence to replace the endogenous coding sequence via homologous recombination in C57BL/6N-derived JM8A3 ES cells. This resulted in an A to G point mutation, which effectively reverts the ahl allele to wild-type. Founders were bred to B6N.Cg-Tg(Sox2-cre)1Amc/J to excise the downstream loxP-flanked PGK-Neo cassette and their offspring were bred to C57BL/6NJ to remove the transgene. Mice heterozygous for this point substitution were intercrossed to homozygosity.
|Allele Name||targeted mutation 2.1, Kenneth R Johnson|
|Allele Type||Targeted (Not Specified)|
|Gene Symbol and Name||Cdh23, cadherin 23 (otocadherin)|
|Strain of Origin||C57BL/6N-Atm1Brd|
|Molecular Note||Chr10: 60,527,162 bp 60,536,889 bp (GRCm38), which contains the functional c.753G variant, was taken from a 129S1-derived BAC, a loxP-flanked PGK-Neo cassette was inserted 178 bp downstream of the c.753 nucleotide, homology arms were added to correctly target this sequence to replace the endogenous coding sequence via homologous recombination in C57BL/6N-derived ES cells, resulting in a A to G point mutation, which effectively reverts the ahl allele to wild-type, with a downstream loxP-flanked PGK-Neo cassette. Subsequent breeding to a cre deleter strain excised the selection cassette and generated this allele.|
When using the B6N(Cg)-Cdh23tm2.1Kjn/Kjn mouse strain in a publication, please cite the originating article(s) and include JAX stock #018399 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.