Waltzer 7 Jackson, a remutation of the Cdh23 gene
Belinda S. Harris, Patricia F. Ward-Bailey, Qing Yin Zheng, Roderick T. Bronson, Kenneth R. Johnson, and Muriel T. Davisson
Source of Support: This research was supported by NIH/NCRR grant RR01183 to the Mouse Mutant Resource (M.T.Davisson, PI) and Cancer Center Core Grant CA34196.
Mutation (allele) symbol: Cdh23v-7J
Mutation (allele) name: waltzer 7 Jackson
Gene symbol: Cdh23
Strain of origin: CbyJ.Cg-Foxn1nu/JCurrent strain name: CByJ(Cg)-Cdh23-v-7J/J
Stock #: 003761 Note: As of 8-18-06 Waltzer 7 Jackson is available as DNA only from the DNA Resource at The Jackson Laboratory.
Phenotype categories: circling, hearing loss, head tossingAbstract
We have identified a new remutation to the cadherin 23v (otocadherin) gene by first mapping the remutation to the region of Chromosome 10 where the mouse mutation waltzer (v) is located and then by performing a direct test for allelism.
Origin and Description
The waltzer 7 Jackson (v-7J) remutation was discovered by Belinda Harris in a research colony of CbyJ.Cg-Foxn1nu/J mice at the Jackson Laboratory in November 1999. Like other waltzer (v) mutant mice, homozygotes show typical circling, head-tossing, deafness, and hyperactivity. All homozygous mutants are deaf. Abnormalities of the inner ear include degeneration of the organ of Corti, spiral ganglion, stria vascularis, and saccular macula, as previously described for other mutations of the cadherin23v gene (MGD, 2005) .
Genetic Analysis
In order to determine the mode of inheritance, a female homozygous for this remutation was mated to an unrelated CAST/Ei male. There were no affected progeny observed in the F1 generation. Mice from this F1 generation were then mated together to produce F2s, and in this cross both affected and unaffected animals were produced, proving that the mutation is recessive.
Using our standard mapping protocols F2s produced from an intercross with CAST/Ei were used to map this remutation to Chromosome 10 in the region where the mouse mutation waltzer is located.
A direct test for allelism was performed by mating a C57BL/J-v2J/J heterozygote with a mouse homozygous for this new remutation. This mating produced 5 progeny, of which 3 were affected with the (v) phenotype, proving the new mutation to be an allele of the cadherin 23 (otocadherin) gene.
Pathology
Routine pathological screening of a homozygote at 8 months of age showed glaucoma in one eye. Abnormalities of the inner ear include degeneration of the organ of Corti, spiral ganglion, stria vascularis, and saccular macula (MGD, 2005) .
All other tissues were normal in appearance.
Hearing as assessed by Auditory Brain Stem testing (ABR) on individual animals showed that all mutants tested were deaf, and all controls had normal hearing.
Eyes screened with an opthalmoscope showed one homozygote had small retinal vessels, which is characteristic of the C57BL/6J background strain and similar to waltzer 2 Jackson (another waltzer allele of cadherin 23 on a C57BL/6J background). An electroretinogram (ERG) done on a homozygote waltzer 7 Jackson at 32 weeks of age was normal, which differs from waltzer 2 Jackson because Cdh23v-2J has age onset reduced rod ERG at one year of age, as well as large areas of retinal depigmentation.
Discussion
We report here a remutation to waltzer that is similar to other waltzer alleles except the ERG is normal in Cdh23v-7J mice, unlike the ERG in Cdh23v-2J, which is on the same background strain.
Acknowledgements
The authors would like to thank Norm Hawes for excellent opthalmalogic screening, Heping Yu for auditory brain stem testing, and Coleen Marden for excellent pathology preparations.
References
MGD
