C57BL/6J-Cdh23^v-8J/J

Stock number: 004764
Product name: waltzer 8 Jackson
Research areas: Neurobiology Research, Sensorineural Research

Description

These mice carry an ENU-induced mutation characterized by a slight head tilt, circling behavior, and deafness.

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.

Detailed description

The mutants were initially detected based on abnormal pre-pulse-inhibition test results. They were subsequently observed to exhibit a slight head tilt and circling behavior (onset at approximately 4 weeks of age), and the mutant line was established based on the overt phenotype. Testing of auditory brainstem responses revealed the mutants (n=4) to be deaf. The vestibular abnormality of nmf112 was mapped as a recessive phenotype in 19 affected and 20 unaffected (C57BL/6J-nmf112 x BALB/cByJ) F2 intercross mice, and the best linkage was to D10Mit138 (LOD = 7.0) and D10Mit15 (LOD = 6.1). Because of the map position of this mutation and its phenotypic similarity to the waltzer mutations, a series of complementation tests was performed to determine if allelic relationships exist between NMF112, NMF181, NMF252 and Cdh23. The results showed NMF112 to be an allele of NMF181 (one mating produced 2 mutants in a total of 7 progeny), of NMF252 (one mating produced 2 mutants in a total of 5 progeny) and therefore of Cdh23, since NMF252 has been identified as a new allele of Cdh23. This information suggests therefore that NMF112 mutants might be useful for studying neurobiological mechanisms related to Usher syndrome and human deafness.

Standard pathology work-up on one mutant that died while undergoing ECT testing (94 days of age) showed signs of otitis. The bones of the inner ear had degenerated, possibly due to chronic otitis. Standard pathological work-up and serial sections of ears on two additional mutants (38 days of age) showed no abnormalities.

Development

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

Symbol: Cdh23^v-8J
Name: waltzer 8 Jackson
MGI accession ID: MGI:2663947
Generation method: Chemically induced (ENU)
Marker symbol: Cdh23
Marker name: cadherin 23 (otocadherin)
Chromosome: 10
Strain of origin: C57BL/6J
Molecular note: The mutant nmf112 has a similar phenotype and mapping position to the waltzer mutant. Complementation testing between nmf112 and a known allele at the waltzer locus, Cdh23^nmf252, confirmed the allelic relationship.

Allele

Symbol: Cdh23^ahl
Name: age related hearing loss 1
MGI accession ID: MGI:3028349
Generation method: Spontaneous
Marker symbol: Cdh23
Marker name: cadherin 23 (otocadherin)
Chromosome: 10
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.