Routine examination for auditory function at 4-5 weeks of age revealed the mutants to be deaf. Acoustic startle response and Auditory brain stem recordings yielded no response at every frequency and intensity tested (click, 8, 16, 32 KHz at 30-90 dB); circling and head tossing behavior can also be observed. Standard pathology work-up on two mutants (428 or 41 days of age) revealed a slight loss of Purkinje cells in the younger mutant. Serial Sections of the ears of the younger mutant showed atrophy in some portions of the organ of Corti. Whole-mount ear exam on the older mutant showed otoconia to be present and no abnormalities. Subsequent characterization in the laboratory of Dr. Kenneth Johnson at The Jackson Laboratory found severe hearing impairment in 6 homozygotes tested at 32 days of age, where ABR analysis showed 35-50 dB threshold elevations relative to controls, and no ABR in 9 homozygotes tested at 70 days of age, even when subjected to the maximum 100 dB stimulus. The Johnson laboratory also performed scanning electron microscopy of mutant cochleae at 30 days of age, showing hair cell bundle abnormalities, and cochlear cross-sections at 6 weeks of age, showing degeneration of the organ of Corti.
The nmf318 mutation was identified in the progeny of an N-ethyl-N-nutrosourea (ENU) treated C57BL/6J male bred to a C57BL/6J female. This mutation was maintained purely on a C57BL/6J background and in 2006 sperm was cryopreserved from homozygous males at generation N3F2.
|Allele Name||neuroscience mutagenesis facility, 318|
|Allele Type||Chemically induced (ENU) (Not Specified)|
|Gene Symbol and Name||Clic5, chloride intracellular channel 5|
|Strain of Origin||C57BL/6J|
|Molecular Note||This ENU-induced single nucleotide substitution c.680T>C (from ATG start, NM-172621) in exon 6 is predicted to change a highly conserved phenylalanine residue at amino acid 227 to serine (NP_766209).|
Due to the circling phenotype this strain is best maintained from heterozygous females bred to homozygous or heterozgyous males.
When using the C57BL/6J-Clic5nmf318/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #005329 in your Materials and Methods section.