Usher syndromes

The Usher syndromes (USH) are a large group of inherited disorders involving both hearing and vision loss.

JAX® Mice models

Adato et al. (2005) wrote an excellent review of the five mutant genes known to be responsible for Usher syndrome. We distribute JAX® Mice models for each:

B6.A-Ush1g js/J

("Jackson Shaker," 000783) for sans

SH1/LeJ

("shaker," 000271) for myosin VIIa,

B6;129S4-Ush1cdfcr-2J/J and BALB/cBy-Ush1cdfcr/J

("deaf circler," 004768 and 004771) for harmonin

B6J x B6.C-H2bm1/ByJ-Cdh23v-J/J and C57BL/6J-Cdh23v-2J/J

("waltzer," 002432 and 002552 respectively) for cadherin 23, and

C57BL/6J-Pcdh15av-3J/J

("Ames waltzer," 002072) for protocadherin 15

All these mutants are deaf, have vestibular dysfunctions, and develop abnormal sensory hair bundles. Below, we compare some of the features of three.

B6J x B6.C-H2bm1/ByJ-Cdh23v-J/J

002432

C57BL/6J-Cdh23v-2J/J

002552

C57BL/6J-Pcdh15av-3J/J

002072

Seven remutations to Ames waltzer (av) have occurred in stocks at The Jackson Laboratory. All homozygotes for these remutations have the head-tossing, circling, and deafness characteristic of Ames waltzer. Ames waltzer 2 Jackson homozygotes (Pcdh15av-2J/Pcdh15av-2J) are more severely afflicted than others. Whereas they become disoriented and sink in swim tests, 1J and 3J homozygotes (Pcdh15av-J/Pcdh15av-J and Pcdh15av-3J/Pcdh15av-3J) homozygotes swim with difficulty and circle afloat. The fluid spaces in the Organ of Corti in these mice fail to develop, and, later, hair cells and spiral ganglion cells degenerate.

References

Adato A, Michel V, Kikkawa Y, Reiners J, Alagramam K, Weil D, Yonekawa H, Wolfrum U, El-Amraoui A, Petit C. 2005. Interactions in the network of Usher syndrome type 1 proteins. Hum Mol Genet 14:347-356.

Alagramam KN, Murcia CL, Kwon HY, Pawlowski KS, Wright CG, Woychik RP. 2001. The mouse Ames waltzer hearing-loss mutant is caused by mutation of Pcdh15, a novel protocadherin gene. Nat Genet 27:99-102.

Bolz H, von Brederlow B, Ramirez A, Bryda EC, Kutsche K, Nothwang HG, Seeliger M, del C-Salcedo Cabrera M, Vila MC, Molina OP, Gal A, Kubisch C. 2001. Mutation of CDH23, encoding a new member of the cadherin gene family, causes Usher syndrome type 1D. Nat Genet 27:108-12.

Di Palma F, Holme RH, Bryda EC, Belyantseva IA, Pellegrino R, Kachar B, Steel KP, Noben-Trauth K. 2001. Mutations in Cdh23, encoding a new type of cadherin, cause stereocilia disorganization in waltzer, the mouse model for Usher syndrome type 1D. Nat Genet 27:103-7.

Hampton LL, Wright CG, Alagramam KN, Battey JF, Noben-Trauth K. 2003. A new spontaneous mutation in the mouse Ames waltzer gene, Pcdh15. Hear Res 180:67-75.

Raphael Y, Kobayashi KN, Dootz GA, Beyer LA, Dolan DF, Burmeister M. 2001. Severe vestibular and auditory impairment in three alleles of Ames waltzer (av) mice. Hear Res 151:237-49.