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Gene Review

Myo15  -  myosin XV

Mus musculus

Synonyms: Myo15a, Unconventional myosin-15, Unconventional myosin-XV, sh-2, sh2
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Disease relevance of Myo15

  • Endbulbs of Held in 7-month old, deaf sh2 mice exhibited fewer synaptic vesicles in the presynaptic ending, the loss of intercellular cisternae, and a hypertrophy of associated postsynaptic densities [1].
  • Mutations of the unconventional myosins genes encoding myosin VI, myosin VIIA and myosin XV cause hearing loss and thus these motor proteins perform fundamental functions in the auditory system [2].

High impact information on Myo15

  • This histopathology suggests that Myo15 is necessary for actin organization in the hair cells of the cochlea [3].
  • Genetic mapping has refined sh2 to a 0.6-cM interval of chromosome 11 [4].
  • On the basis of conserved synteny, mouse deafness mutations shaker-2 (sh2) and sh2J are proposed as models of DFNB3 [4].
  • The pirouette (pi) mouse also exhibits deafness and an inner ear pathology resembling that of Myo15 mutant mice and thus may be functionally related to Myo15 [5].
  • These data suggest that the function of Myo15 is distinct from that of Myo6, Myo7a or pi in development and/or maintenance of stereocilia [5].

Biological context of Myo15

  • The shaker 2(J) lesion, in contrast, is a 14.7 kb deletion that removes the last six exons from the 3"-terminus of the Myo15 transcript [6].
  • The shaker 2 allele is a previously described missense mutation of a highly conserved residue in the motor domain of myosin XV [6].
  • These mice carry a point mutation on chromosome 11, affecting myosin 15 and producing abnormally short stereocilia in hair cells of the inner ear [1].
  • Mutant alleles of a third unconventional myosin, myosin XV, are associated with nonsyndromic, recessive, congenital deafness DFNB3 on human chromosome 17p11.2 and deafness in shaker2 (Myo15(sh2)) mice [2].
  • Transgene correction maintains normal cochlear structure and function in 6-month-old Myo15a mutant mice [7].

Anatomical context of Myo15


Other interactions of Myo15

  • Vibrator (gene symbol vb), an autosomal recessive mutation, occurred spontaneously in the DBA/2J strain of mice, was rescued by a single cross to C57BL/6J and subsequent brother X sister mating, and has been mapped near shaker-2 (sh-2) and vestigial tail (vt) on chromosome 11 [9].

Analytical, diagnostic and therapeutic context of Myo15

  • In addition, excess Myo15a expression has no physiologically significant protective or deleterious effects on hearing of normal mice, suggesting that the dosage of Myo15a may not be problematic for gene therapy [7].


  1. Effects of congenital deafness in the cochlear nuclei of Shaker-2 mice: an ultrastructural analysis of synapse morphology in the endbulbs of Held. Lee, D.J., Cahill, H.B., Ryugo, D.K. J. Neurocytol. (2003) [Pubmed]
  2. Unconventional myosins and the genetics of hearing loss. Friedman, T.B., Sellers, J.R., Avraham, K.B. Am. J. Med. Genet. (1999) [Pubmed]
  3. Correction of deafness in shaker-2 mice by an unconventional myosin in a BAC transgene. Probst, F.J., Fridell, R.A., Raphael, Y., Saunders, T.L., Wang, A., Liang, Y., Morell, R.J., Touchman, J.W., Lyons, R.H., Noben-Trauth, K., Friedman, T.B., Camper, S.A. Science (1998) [Pubmed]
  4. Genetic mapping refines DFNB3 to 17p11.2, suggests multiple alleles of DFNB3, and supports homology to the mouse model shaker-2. Liang, Y., Wang, A., Probst, F.J., Arhya, I.N., Barber, T.D., Chen, K.S., Deshmukh, D., Dolan, D.F., Hinnant, J.T., Carter, L.E., Jain, P.K., Lalwani, A.K., Li, X.C., Lupski, J.R., Moeljopawiro, S., Morell, R., Negrini, C., Wilcox, E.R., Winata, S., Camper, S.A., Friedman, T.B. Am. J. Hum. Genet. (1998) [Pubmed]
  5. Myo15 function is distinct from Myo6, Myo7a and pirouette genes in development of cochlear stereocilia. Karolyi, I.J., Probst, F.J., Beyer, L., Odeh, H., Dootz, G., Cha, K.B., Martin, D.M., Avraham, K.B., Kohrman, D., Dolan, D.F., Raphael, Y., Camper, S.A. Hum. Mol. Genet. (2003) [Pubmed]
  6. The motor and tail regions of myosin XV are critical for normal structure and function of auditory and vestibular hair cells. Anderson, D.W., Probst, F.J., Belyantseva, I.A., Fridell, R.A., Beyer, L., Martin, D.M., Wu, D., Kachar, B., Friedman, T.B., Raphael, Y., Camper, S.A. Hum. Mol. Genet. (2000) [Pubmed]
  7. Transgene correction maintains normal cochlear structure and function in 6-month-old Myo15a mutant mice. Kanzaki, S., Beyer, L., Karolyi, I.J., Dolan, D.F., Fang, Q., Probst, F.J., Camper, S.A., Raphael, Y. Hear. Res. (2006) [Pubmed]
  8. Age-related changes in cochlear gene expression in normal and shaker 2 mice. Gong, T.W., Karolyi, I.J., Macdonald, J., Beyer, L., Raphael, Y., Kohrman, D.C., Camper, S.A., Lomax, M.I. J. Assoc. Res. Otolaryngol. (2006) [Pubmed]
  9. Vibrator (vb): a spinocerebellar system degeneration with autosomal recessive inheritance in mice. Weimar, W.R., Lane, P.W., Sidman, R.L. Brain Res. (1982) [Pubmed]
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