C57BL/6J-nmf118/J

Stock number: 004747
Research areas: Neurobiology Research, Sensorineural Research

Description

These mice carry an ENU-induced mutation and are characterized by small body size, body tremors, slightly abnormal movement of hind limbs, and hearing abnormalities.

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 are small, show body tremor, and slightly abnormal movement of hind limbs; toes are frequently curled and the foot pads do not make proper contact with the ground. In addition, abnormal results in two phenotypic screens were observed: grip strength and auditory brainstem response (ABR). Of two mutants tested for grip strength, one showed reduced values, and of four mutants tested for ABR, two were deaf, one showed reduced hearing ability at 16 and 32 Hz, and one tested normal. These results, combined with the pathology findings, suggest that these are mutants with hearing abnormalities.

Standard pathology work-up on two mutants (110 or 150 days of age) showed degenerating muscle fibers mixed with giant fibers in the

spinal muscle.

A deficiency of neurons in the

spiral ganglia (

normal spinal ganglia)

and an absence of hair cells were noted in the ear. Standard pathology performed on a much younger mutant (36 days of age) revealed 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: nmf118
Name: neuroscience mutagenesis facility, 118
MGI accession ID: MGI:2663969
Generation method: Chemically induced (ENU)
Marker symbol: nmf118
Marker name: neuroscience mutagenesis facility, 118
Chromosome: 10
Strain of origin: C57BL/6J
Molecular note: This phenotypic mutant was identified in an ENU mutagenesis screen.

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.