Mice homozygous for the Ush1ctm1Xzl mutation have circling, head-tossing, and hyperactive behaviors typical of vestibular mutants. Auditory-evoked brainstem assessment shows that homozygotes are completely deaf and scanning electron microscopy shows that the hair cell stereocilia become progressively disorganized with age, with the outer hair cells more affected than the inner hair cells. Although histology at 12 months of age does not reveal any abnormalities, there is a decline in electrotreinogram readings for both rods and cones by 11 months of age. Because the first four exons were replaced by the beta galactosidase reporter cassette, endogenous expression of this gene in phenotypically normal mice can be traced by assessing lacZ expression in heterozygotes.
The Ush1ctm1Xzl targeted mutation was generated at The Jackson Laboratory via homologous recombination in R1 ES cells, which derive from (129X1/SvJ x 129S1/Sv)F1-Kitl+ mice. The chimeric founder was bred with C57BL/6J and the mutation was backcrossed onto C57BL/6J for 11 generations and then intercrossed and maintained primarily by sibling mating heterozygotes to homozygotes.
|Allele Name||targeted mutation 1, Xue Liu|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Ush1c, USH1 protein network component harmonin|
|Strain of Origin||(129X1/SvJ x 129S1/Sv)F1-Kitl+|
|Molecular Note||The first four exons were replaced with a Beta galactosidase reporter and neomycin resistance genes, successfully eliminating expression of all of the many transcripts produced by this gene, including a, b, and c isoforms.|