Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Normal hearing in Splotch (Sp/+), the mouse homologue of Waardenburg syndrome type 1

Nature Genetics volume 2, pages 75–79 (1992)Cite this article

Abstract

Splotch is considered a model of Waardenburg syndrome type I (WSI) because the abnormalities are caused by mutations in homologous genes, Pax–3 in mice and PAX3 (HuP2) in humans. We examined inner ear structure and function in Splotch mutants (Sp/+) and found no sign of auditory defects, in contrast to the deafness in many WSI individuals. The difference in expression of the genes in the two species may be due to different parts of the gene being mutated, or may result from variations in modifying influences as yet undefined.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Newton, V. Hearing loss and Waardenburg's syndrome: Implications for genetic counselling. J. Laryng. Otol. 104, 97–103 (1990).

    Article  CAS  Google Scholar 

  2. Hageman, M.J. & Delleman, J W Heterogeneity in Waardenburg syndrome. Am. J. hum. Genet. 29, 468–485 (1977).

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Farrer, L.A., et al. Waardenburg syndrome (WS) type I is caused by defects at multiple loci, one of which is near ALPP on chromosome 2: First report of the WS Consortium. Am. J. hum. Genet. 50, 902–913 (1992).

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Asher, J.H. & Friedman, T.B. Mouse and hamster mutants as models for Waardenburg syndromes in humans. J. med. Genet. 27, 618–626. (1990).

    Article  Google Scholar 

  5. Foy, C., Newton, V., Wellesley, D., Harris, R. & Read, A.P. Assignment of the locus for Waardenburg syndrome type 1 to human chromosome 2q37 and possible homology to the Splotch mouse. Am. J. hum. Genet. 46, 1017–1023 (1990).

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Auerbach, R. Analysis of the developmental effects of a lethal mutation in the house mouse. J. exp. Zool. 127, 305–329 (1954).

    Article  Google Scholar 

  7. Deol, M.S. Influence of the neural tube on the differentiation of the inner ear in the mammalian embryo. Nature 209, 219–220 (1966).

    Article  CAS  Google Scholar 

  8. Epstein, D.J., Vekemans, M. & Gros, P. Splotch (Sp2H), a mutation affecting development of the mouse neural tube, shows a deletion within the paired homeodomain of Pax-3. Cell 67, 767–774 (1991).

    Article  CAS  Google Scholar 

  9. Goulding, M.D., Chalepakis, G., Deutsch, U., Erselius, J.R. & Gruss, P. Pax-3, a novel murine DNA binding protein expressed during early neurogenesis. EMBO J. 10, 1135–1147 (1991).

    Article  CAS  Google Scholar 

  10. Tassabehji, M., et al. Waardenburg's syndrome patients have mutations in the human homologue of the Pax-3 paired box gene. Nature 355, 635–636 (1992).

    Article  CAS  Google Scholar 

  11. Baldwin, C.T., Hoth, C.F., Amos, J.A., da-Silva, E.O. & Milunsky, A. An exonic mutation in the HuP2 paired domain gene causes Waardenburg's syndrome. Nature 355, 637–638 (1992).

    Article  CAS  Google Scholar 

  12. Burri, M., Tromvoukis, Y., Bopp, D., Frigerio, G. & Noll, M. Conservation of the paired domain in metazoans and its structure in three isolated human genes. EMBO J. 8, 1183–1190 (1989).

    Article  CAS  Google Scholar 

  13. Johnstone, J.R., Alder, V.A., Johnstone, B.M., Robertson, D. & Yates, G.K. Cochlear action potential threshold and single unit thresholds. J. Acoust. Soc. Am. 65, 254–257 (1979).

    Article  CAS  Google Scholar 

  14. Patuzzi, R.B., Yates, G.K. & Johnstone, B.M. The origin of the low-frequency microphonic in the first cochlear turn of guinea-pig. Hearing Res. 39, 177–188 (1989).

    Article  CAS  Google Scholar 

  15. Rarey, K.E. & Davis, L.E. Inner ear anomalies in Waardenburg's syndrome associated with Hirschsprung's disease. Int. J. Pediat. Otorhinolaryngol. 8, 181–189 (1984).

    Article  CAS  Google Scholar 

  16. Fisch, L. (1959) Deafness as part of an hereditary syndrome. J. Lar. Otol. 73, 355–383.

    Article  CAS  Google Scholar 

  17. Nemansky, J. & Hageman, M.J. Tomographic findings of the inner ears of 24 patients with Waardenburg's syndrome. Am. J. Roentgenol. Radium Ther. Nucl. Med. 124, 250–255 (1975).

    Article  CAS  Google Scholar 

  18. Marcus, R.E. Recognition and diagnosis of hereditary deafness with tomographic correlates. Tr. Am. Acad. Ophth. 73, 409–419 (1969).

    CAS  Google Scholar 

  19. Marcus, R.E. & Valvassori, G. Cochleo-vestibular apparatus: radiologic studies in hereditary and familial hearing loss. Int. Audiol. 9, 95–102 (1970).

    Article  Google Scholar 

  20. Jensen, J. Tomography of inner ear in case of Waardenburg's syndrome. Am. J. Roentgenol., Rad. Ther. Nuclear Med. 101, 828–833 (1967).

    Article  CAS  Google Scholar 

  21. Irie, K., Ogata, H. & Mitsudome, A. CT findings of the temporal bones in Waardenburg's syndrome. No To Hattatsu 22, 241–246 (1990).

    CAS  PubMed  Google Scholar 

  22. Hageman, M.J. & Oosterveld, W.J. Vestibular findings in 25 patients with Waardenburg's syndrome. Arch. Otolaryngol. 103, 648–652 (1977).

    Article  CAS  Google Scholar 

  23. Galich, R. Temporal bone involvement in Waardenburg's syndrome. Ear, Nose Throat J. 64, 441–445 (1985).

    CAS  Google Scholar 

  24. Hildesheimer, M., Maayan, Z., Muchnik, C., Rubinstein, M. & Goodman, R.M. Auditory and vestibular findings in Waardenburg's type II syndrome. J. Lar. Otol. 103, 1130–1133 (1989).

    Article  CAS  Google Scholar 

  25. Deol, M.S. Genetic malformations of the inner ear in the mouse and in man. Birth Defects: Original article series 16, 243–261 (1980).

    CAS  Google Scholar 

  26. Wright, J.L.W., Phelps, P.O. & Friedmann, I. Temporal bone studies in anencephaly. J. Lar. Otol. 90, 919–927 (1976).

    Article  CAS  Google Scholar 

  27. Steel, K.P. & Bock, G.R. Hereditary inner ear abnormalities in animals. Relationship with human abnormalities. Arch. Otolaryngol. 109, 22–29 (1983).

    Article  CAS  Google Scholar 

  28. Kapron-Bras, C.M. & Trasler, D.G. Reduction in the frequency of neural tube defects in Splotch mice by retinoic acid. Teratology 32, 87–92 (1985).

    Article  CAS  Google Scholar 

  29. Steel, K.P., Barkway, C. & Bock, G.R. Strial dysfunction in mice with cochleo-saccular abnormalities. Hearing Res. 27, 11–26 (1987).

    Article  CAS  Google Scholar 

  30. Steel, K.P. & Barkway, C. Another role for melanocytes: their importance for normal stria vascularis development in the mammalian inner ear. Development 107, 453–463 (1989).

    CAS  PubMed  Google Scholar 

  31. Hulten, M.A., Honeyman, M.M., Mayne, A.J. & Tarlow, M.J. Homozygosity in piebald trait. J. Med. Genet. 24, 568–571 (1987).

    Article  CAS  Google Scholar 

  32. Morell, R. et al. A frameshift mutation in the HuP2 paired domain of the probable human homolog of murine Pax-3 is responsible for Waardenburg Syndrome Type 1 in an Indonesian family. Human molec. Genet. (in the press).

  33. Kuehn, M.R., Bradley, A., Robertson, E.J. & Evans, M.J.A. potential animal model for Lesch-Nyhan syndrome through introduction of HPRT mutations into mice. Nature 326, 295–298 (1987).

    Article  CAS  Google Scholar 

  34. Hoffman, E.P., Brown, R.H. & Kunkel, L.M. Dystrophin: The protein product of the Duchenne muscular dystrophy locus. Cell 51, 919–928 (1987).

    Article  CAS  Google Scholar 

  35. Konyukhov, B.V. & Mironova, O.V. Interaction of the mutant genes splotch and fidget in mice. Soviet Genet. 15, 407–411 (1979).

    Google Scholar 

  36. Moase, C.E. & Trasler, D.G. Splotch locus mouse mutants: models for neural tube defects and Waardenburg syndrome type I in humans. J. med. Genet. 29, 145–151 (1992).

    Article  CAS  Google Scholar 

  37. Henry, K.R. & Lepkowski, C.M. Evoked potential correlates of genetic progressive hearing loss. Acta Otolaryng. 86, 366–374 (1978).

    CAS  PubMed  Google Scholar 

  38. Walther, C. & Gruss, P. Pax-6, a murine paired box gene, is expressed in the developing CNS. Development 113, 1435–1449 (1991).

    CAS  Google Scholar 

  39. Deutsch, U. & Gruss, P. Murine paired domain proteins as regulatory factors of embryonic development. Sem. devel. Biol. 2, 413–424 (1991).

    Google Scholar 

  40. Chalepakis, G. et al. The molecular basis of the undulated/Pax-1 mutation. Cell 66, 873–884 (1991).

    Article  CAS  Google Scholar 

Download references

Author information

Author notes

  1. Richard J.H. Smith

    Present address: Department of Otolaryngology, University of Iowa, Iowa City, Iowa, 52242, USA

Authors and Affiliations

  1. MRC Institute of Hearing Research, University Park, Nottingham, NG7 2RD, UK

    Karen P. Steel & Richard J.H. Smith

Authors
  1. Karen P. Steel
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Richard J.H. Smith
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Steel, K., Smith, R. Normal hearing in Splotch (Sp/+), the mouse homologue of Waardenburg syndrome type 1. Nat Genet 2, 75–79 (1992). https://doi.org/10.1038/ng0992-75

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ng0992-75

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing