Subscribe to RSS
DOI: 10.1055/s-2003-39838
Mouse Genetics as a Tool for Elucidating Molecular Pathways Involved in Hearing Loss
Publication History
Publication Date:
11 June 2003 (online)
ABSTRACT
The identification of genes responsible for hereditary hearing loss allows us to understand these diseases at the molecular level with the potential of revealing mechanisms and pathways important in auditory function. As is the case in other human diseases, the importance of the mouse as a model in hearing research is increasing. Several genes identified in mouse mutants already have led to the identification of human deafness genes. The existence of phenotypic variations within a population carrying the same disease mutation indicates genetic modification of the phenotype by other loci. Identification of these modifiers will further our understanding of the biochemical and regulatory pathways through which the deafness disease genes act.
KEYWORDS
Genetics - hearing - modifier - tubby - deaf waddler
REFERENCES
- 1 van Laer L, McGuirt W T, Yang T, Smith R J, van Camp G. Autosomal dominant nonsyndromic hearing impairment. Am J Med Genet . 1999; 89 167-174
- 2 Sundstrom R A, van Laer L, van Camp G, Smith R J. Autosomal recessive nonsyndromic hearing loss. Am J Med Genet . 1999; 89 123-129
- 3 Willems P J. Genetic causes of hearing loss. N Engl J Med . 2000; 342 1101-1109
- 4 Van Camp G, Smith R J. Maternally inherited hearing impairment. Clin Genet . 2000; 57 409-414
- 5 Steel K P, Kros C J. A genetic approach to understanding auditory function. Nat Genet . 2001; 27 143-149
- 6 Zheng Q Y, Johnson K R, Erway L C. Homepage. Hereditary Hearing Impairment in Mice [on-line] 2001; available: http://www.jax.org/research/hhim/
- 7 Probst F J, Camper S A. The role of mouse mutants in the identification of human hereditary hearing loss genes. Hear Res . 1999; 130 1-6
- 8 Di Palma F, Holme R H, Bryda E C. Mutations in CdH23, encoding a new type of cadherin, cause stereocilia disorganization in waltzer, the mouse model for Usher syndrome type 1D. Nat Genet . 2001; 27 103-107
- 9 Balciuniene J, Dahl N, Jalonen P. Alpha-tectorin involvement in hearing disabilities: one gene-two phenotypes. Hum Genet . 1999; 105 211-216
- 10 Riazuddin S, Castelein C M, Ahed Z M. Dominant modifier DFNM1 suppresses recessive deafness DFNB26. Nat Genet . 2000; 26 431-433
- 11 Salam A A, Hafner F M, Linder T E. A novel locus (DFNA23) for prelingual autosomal dominant nonsyndromic hearing loss maps to 14q21-q22 in a Swiss German kindred. Am J Hum Genet . 2000; 66 1984-1988
- 12 Cohn E S, Kelley P M, Fowler T W. Clinical studies of families with hearing loss attributable to mutations in the connexin 26 gene (GJB2/DFNB1). Pediatrics . 1999; 103 546-550
- 13 Friedman T, Battey J, Kachar B. Modifiers of hereditary hearing loss. Curr Opin Neurobiol . 2000; 10 487-493
- 14 Steel K P. Inherited hearing defects in mice. Annu Rev Genet . 1995; 29 675-701
- 15 Noben-Trauth K, Zheng Q Y, Johnson K R, Nishina P M. mdfw: a deafness susceptibility locus that interacts with deaf waddler (dfw). Genomics . 1997; 44 266-272
- 16 Street V A, McKee-Johnson J W, Fonseca R C, Tempel B L, Noben-Trauth K. Mutations in a plasma membrane Ca2+-ATPase gene cause deafness in deafwaddler mice. Nat Genet . 1998; 19 390-394
- 17 Johnson K R, Erway L C, Cook S A, Willott J F, Zheng Q Y. A major gene affecting age-related hearing loss in C57BL/6J mice.Hear Res . 1997; 114 83-92
- 18 Zheng Q Y, Johnson K R. Hearing loss associated with the modifier of deaf waddler (mdfw) locus corresponds with age-related hearing loss in 12 inbred strains of mice. Hear Res . 2001; 154 45-53
- 19 Johnson K R, Zheng Q Y, Bykhovskaya Y, Spirina O, Fischel-Ghodsian N. A nuclear-mitochondrial DNA interaction affecting hearing impairment in mice. Nat Genet . 2001; 27 191-194
- 20 Coleman D L, Eicher E M. Fat (fat) and tubby (tub): two autosomal recessive mutations causing obesity syndromes in the mouse. J Hered . 1990; 81 424-427
- 21 Heckenlively J R, Chang B, Erway L C. Mouse model for Usher syndrome: linkage mapping suggests homology to Usher type I reported at human chromosome 11p15. Proc Natl Acad Sci U S A . 1995; 92 11100-11104
- 22 Ohlemiller K K, Hughes R M, Lett J M. Progression of cochlear and retinal degeneration in the tubby (rd5) mouse. Audiol Neurootol . 1997; 2 175-185
- 23 Collin G B, Marshall J D, Cardon L R, Nishina P M. Homozygosity mapping at Alstrom syndrome to chromosome 2p. Hum Mol Genet . 1997; 6 213-219
- 24 Ikeda A, Zheng Q Y, Rosenstiel P. Genetic modification of hearing in tubby mice: evidence for the existence of a major gene (motH1) which protects tubby mice from hearing loss. Hum Mol Genet . 1999; 8 1761-1767
- 25 Noben-Trauth K, Naggert J K, North M A, Nishina P M. A candidate gene for the mouse mutation tubby. Nature . 1996; 380 534-538
- 26 Kleyn P W, Fan W, Kovats S G. Identification and characterization of the mouse obesity gene tubby: a member of a novel gene family. Cell . 1996; 85 281-290
- 27 Kapeller R, Moriarty A, Strauss A. Tyrosine phosphorylation of tuband its association with Src homology 2 domain-containing proteins implicate tub in intracellular signaling by insulin. J Biol Chem . 1999; 274 24980-24986
- 28 Boggon T J, Shan W S, Santagata S, Myers S C, Shapiro L. Implication of tubby proteins as transcription factors by structure-based functional analysis. Science . 1999; 286 2119-2125
- 29 Hagstrom S A, Duyao M, North M A, Li T. Retinal degeneration in tulp1-/- mice: vesicular accumulation in the interphotoreceptor matrix. Invest Ophthalmol Vis Sci . 1999; 40 2795-2802
- 30 He W, Ikeda S, Bronson R T. GFP-tagged expression and immunohistochemical studies to determine the subcellular localization of the tubby gene family members. Brain Res Mol Brain Res . 2000; 81 109-117
- 31 Moore K J, Nagle D L. Complex trait analysis in the mouse: the strength, the limitations and the promise yet to come. Annu Rev Genet . 2000; 34 653-686
- 32 Darvasi A. Experimental strategies for the genetic dissection of complex traits in animal models. Nat Genet . 1998; 18 19-24
- 33 Ikeda A, Zheng Q Y, Zuberi A R. Microtubule-associated protein 1A is a modifier of tubby hearing (motH1). Nat Genet . 2002; 30 401-405
- 34 Brenman J E, Topinka J R, Cooper E C. Localization of postsynaptic density-93 to dendritic microtubules andinteraction with microtubule-associated protein 1A. J Neurosci . 1998; 18 8805-8813
- 35 Thomas U, Ebitsch S, Gorczyca M. Synaptic targeting and localization of Disc-large is a stepwise process controlled by different domains of the protein. Curr Biol . 2000; 10 1108-1117