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
Genetic Background | Generation |
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Allele Type | Gene Symbol | Gene Name |
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Targeted (Not Specified) | Cdh23 | cadherin 23 (otocadherin) |
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 |
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Allele Type | Targeted (Not Specified) |
Allele Synonym(s) | Cdh23c.735G |
Gene Symbol and Name | Cdh23, cadherin 23 (otocadherin) |
Gene Synonym(s) | |
Strain of Origin | C57BL/6N-Atm1Brd |
Chromosome | 10 |
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.
Facility Barrier Level Descriptions
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Heterozygous for Cdh23<tm2.1Kjn> |
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