These mice carry an ENU-induced mutation characterized by dystrophic axons and abnormal muscle fibers.
The Jackson Laboratory cannot guarantee that cryorecovery of strains from the discontinued NIH-funded Neuroscience Mutagenesis Facility (NMF) will be successful or that the anticipated phenotype or genotype will be obtained. The cryorecovery fee for this effort will not be refunded or prorated if the recovery is unsuccessful or is in any way unsatisfactory. Genotyping will be the responsibility of the Purchaser.Read More +
The C57BL/6J background strain is homozygous for the age related hearing loss mutation Cdh23ahl, which on this background causes progressive hearing loss with onset after 10 months of age.
The mutants are small and exhibit an unsteady gait, which can be detected at 4 weeks of age (+/- 0.48; n=21). A colony can be maintained through heterozygote matings. Two female mutants tested showed weights slightly (approximately 10%) below normal. Two mutants were tested for Fear-potentiated-startle and Acoustic startle response, and for each screen one mutant showed abnormal, one normal results. Unaffected littermates showed normal results (n=5). Similarly, auditory brainstem responses (at 6 weeks of age) showed one mutant to be deaf and one to be severely hearing impaired (only a late response to a 8kHz stimulus at 90db was observed), while two unaffected littermates tested normal.
Standard pathology work-up on 3 mutants (113 - 161 days of age) showed dystrophic axons and a few abnormal muscle fibers. Large lobules of lymphocytes in the lung and mild hydrocephaly were also present in one mutant. Retinal degeneration, and a loss of hair cells, supporting cells and ganglionic cells of the ear were also observed in the oldest mutant.
This phenotypic deviant was generated by ethylnitrosourea (ENU) mutagenesis in C57BL/6J males (Stock No. 000664), in the Neuroscience Mutagenesis facility at The Jackson Laboratory. Mutagenized males were crossed to C57BL/6J females; G3 descendants of the mutagenized males were selected for neurological impairment.
|Allele Name||neuroscience mutagenesis facility, 110|
|Allele Type||Chemically induced (ENU)|
|Gene Symbol and Name||nmf110, neuroscience mutagenesis facility, 110|
|Strain of Origin||C57BL/6J|
|Molecular Note||This phenotypic mutant was identified in an ENU mutagenesis screen.|
|Allele Name||age related hearing loss 1|
|Allele Synonym(s)||Cdh23753A; mdfw|
|Gene Symbol and Name||Cdh23, cadherin 23 (otocadherin)|
|Strain of Origin||multiple strains|
|Molecular Note||Genetic complementation tests have shown allelism between the mdfw (modifier of deaf waddler) locus and the ahl locus. Further analysis has shown this is caused by a G to A transition at coding nucleotide position 753 of Cdh23 (SNP rs257098870). This hypomorphic allele changes splice donor site G-GT to A-GT, causing frame skipping of exon 7. This is predicted to delete part of the 2nd and 3rd ectodomains and cause reduced message stability. Twenty-seven strains classified with ahl and carrying the 753A allele include: CD-1, RBF/DnJ, PL/J, AKR/J, RF/J, BALB/cBy, A/WySnJ, P/J, SENCARA/PtJ, DBA/1J, ALS/LtJ, C58/J, C57BLKS/J, 129P1/ReJ, C57BR/cd, SKH2/J, BUB/Bn, MA/MyJ, LP/J, 129X1/SvJ, NOR/LtJ, A/J, C57BL/6, NOD/LtJ, DBA/2J, ALR/LtJ, C57L/J. Strains classified with ahl that DO NOT carry this mutation include: 129S1/SvImJ, C3H/HeSnJ, I/LnJ, YBR/Ei, MRL/MpJ.|