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Salt-inducible kinase 3, SIK3, is a new gene associated with hearing.

Wolber LE, Girotto G, Buniello A, Vuckovic D, Pirastu N, Lorente-Cánovas B, Rudan I, Hayward C, Polasek O, Ciullo M, Mangino M, Steves C, Concas MP, Cocca M, Spector TD, Gasparini P, Steel KP, Williams FM - Hum. Mol. Genet. (2014)

Bottom Line: In this study, genome-wide association results of hearing function from the G-EAR consortium and TwinsUK were used for meta-analysis.A single SNP lying in intron 6 of the salt-inducible kinase 3 (SIK3) gene was found to be associated with hearing PC2 (P = 3.7×10(-8)) and further supported by whole-genome sequence in a subset.Our results suggest a developmental role of Sik3 in hearing and may be required for the maintenance of adult auditory function.

View Article: PubMed Central - PubMed

Affiliation: Department of Twin Research and Genetic Epidemiology, King's College London, London SE1 7EH, UK.

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Related in: MedlinePlus

Sik3 is expressed in cochlear structures at different developmental stages. Mouse cochlear sections were stained with primary Sik3 antibody (brown) and counterstained with haematoxylin (blue). A, B, E and F: at the day of birth (P0), Sik3 expression was detected in the apex of inner and outer hair cells (B, red arrows), in the perilymph-facing layer of the Reissner's membrane (F, grey arrows), near blood vessels of the intermediate layer of the stria vascularis (F, black arrows), as well as in cells of the spiral ganglion (E, white arrows) and cells surrounding the ganglion. C, D, G and H: at 5 days postnatal (P5), Sik3 expression was found in the hair cells (D, red arrows) and small cells of the spiral ganglion (G, white arrows). I and J: at 4 weeks postnatal, Sik3 expression remained in the spiral ganglion (J, white arrows), Reissner's membrane and stria vascularis but could not be detected in the apex of the hair cells (I). K, L and M: confocal imaging of Sik3 expression in the stereocilia at 5 days postnatal (L, green), compared with Phalloidin expression (K, red) showed that Sik3 was expressed in the region around the base of the stereocilia (M, merged image of K and L). IHCs, inner hair cells; OHCs, outer hair cells. Scale bars: A, C and I: 50 µm; B, D, E, F, G, H and J: 10 µm; K, L and M: 5 µm.
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DDU346F3: Sik3 is expressed in cochlear structures at different developmental stages. Mouse cochlear sections were stained with primary Sik3 antibody (brown) and counterstained with haematoxylin (blue). A, B, E and F: at the day of birth (P0), Sik3 expression was detected in the apex of inner and outer hair cells (B, red arrows), in the perilymph-facing layer of the Reissner's membrane (F, grey arrows), near blood vessels of the intermediate layer of the stria vascularis (F, black arrows), as well as in cells of the spiral ganglion (E, white arrows) and cells surrounding the ganglion. C, D, G and H: at 5 days postnatal (P5), Sik3 expression was found in the hair cells (D, red arrows) and small cells of the spiral ganglion (G, white arrows). I and J: at 4 weeks postnatal, Sik3 expression remained in the spiral ganglion (J, white arrows), Reissner's membrane and stria vascularis but could not be detected in the apex of the hair cells (I). K, L and M: confocal imaging of Sik3 expression in the stereocilia at 5 days postnatal (L, green), compared with Phalloidin expression (K, red) showed that Sik3 was expressed in the region around the base of the stereocilia (M, merged image of K and L). IHCs, inner hair cells; OHCs, outer hair cells. Scale bars: A, C and I: 50 µm; B, D, E, F, G, H and J: 10 µm; K, L and M: 5 µm.

Mentions: Sik3 was highly expressed at all three developmental stages studied in the mouse: at the day of birth as well as 5 days postnatal, expression of Sik3 was limited to the tops of the inner and outer hair cells in the cochlea, non-neuronal cells of the spiral ganglion, cells in the intermediate layer of the stria vascularis and the perilymph-facing layer of the Reissner's membrane (Fig. 3). In the stria vascularis, Sik3 was expressed near blood vessels in the intermediate layer. These cells have previously been described as macrophage-like melanocytes (25). At 4 weeks after birth, Sik3 expression could no longer be detected in the hair cells, indicating that this expression was limited to early developmental stages. Expression in the spiral ganglion and stria vascularis remained even 4 weeks after birth (Fig. 3).Figure 3.


Salt-inducible kinase 3, SIK3, is a new gene associated with hearing.

Wolber LE, Girotto G, Buniello A, Vuckovic D, Pirastu N, Lorente-Cánovas B, Rudan I, Hayward C, Polasek O, Ciullo M, Mangino M, Steves C, Concas MP, Cocca M, Spector TD, Gasparini P, Steel KP, Williams FM - Hum. Mol. Genet. (2014)

Sik3 is expressed in cochlear structures at different developmental stages. Mouse cochlear sections were stained with primary Sik3 antibody (brown) and counterstained with haematoxylin (blue). A, B, E and F: at the day of birth (P0), Sik3 expression was detected in the apex of inner and outer hair cells (B, red arrows), in the perilymph-facing layer of the Reissner's membrane (F, grey arrows), near blood vessels of the intermediate layer of the stria vascularis (F, black arrows), as well as in cells of the spiral ganglion (E, white arrows) and cells surrounding the ganglion. C, D, G and H: at 5 days postnatal (P5), Sik3 expression was found in the hair cells (D, red arrows) and small cells of the spiral ganglion (G, white arrows). I and J: at 4 weeks postnatal, Sik3 expression remained in the spiral ganglion (J, white arrows), Reissner's membrane and stria vascularis but could not be detected in the apex of the hair cells (I). K, L and M: confocal imaging of Sik3 expression in the stereocilia at 5 days postnatal (L, green), compared with Phalloidin expression (K, red) showed that Sik3 was expressed in the region around the base of the stereocilia (M, merged image of K and L). IHCs, inner hair cells; OHCs, outer hair cells. Scale bars: A, C and I: 50 µm; B, D, E, F, G, H and J: 10 µm; K, L and M: 5 µm.
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Related In: Results  -  Collection

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DDU346F3: Sik3 is expressed in cochlear structures at different developmental stages. Mouse cochlear sections were stained with primary Sik3 antibody (brown) and counterstained with haematoxylin (blue). A, B, E and F: at the day of birth (P0), Sik3 expression was detected in the apex of inner and outer hair cells (B, red arrows), in the perilymph-facing layer of the Reissner's membrane (F, grey arrows), near blood vessels of the intermediate layer of the stria vascularis (F, black arrows), as well as in cells of the spiral ganglion (E, white arrows) and cells surrounding the ganglion. C, D, G and H: at 5 days postnatal (P5), Sik3 expression was found in the hair cells (D, red arrows) and small cells of the spiral ganglion (G, white arrows). I and J: at 4 weeks postnatal, Sik3 expression remained in the spiral ganglion (J, white arrows), Reissner's membrane and stria vascularis but could not be detected in the apex of the hair cells (I). K, L and M: confocal imaging of Sik3 expression in the stereocilia at 5 days postnatal (L, green), compared with Phalloidin expression (K, red) showed that Sik3 was expressed in the region around the base of the stereocilia (M, merged image of K and L). IHCs, inner hair cells; OHCs, outer hair cells. Scale bars: A, C and I: 50 µm; B, D, E, F, G, H and J: 10 µm; K, L and M: 5 µm.
Mentions: Sik3 was highly expressed at all three developmental stages studied in the mouse: at the day of birth as well as 5 days postnatal, expression of Sik3 was limited to the tops of the inner and outer hair cells in the cochlea, non-neuronal cells of the spiral ganglion, cells in the intermediate layer of the stria vascularis and the perilymph-facing layer of the Reissner's membrane (Fig. 3). In the stria vascularis, Sik3 was expressed near blood vessels in the intermediate layer. These cells have previously been described as macrophage-like melanocytes (25). At 4 weeks after birth, Sik3 expression could no longer be detected in the hair cells, indicating that this expression was limited to early developmental stages. Expression in the spiral ganglion and stria vascularis remained even 4 weeks after birth (Fig. 3).Figure 3.

Bottom Line: In this study, genome-wide association results of hearing function from the G-EAR consortium and TwinsUK were used for meta-analysis.A single SNP lying in intron 6 of the salt-inducible kinase 3 (SIK3) gene was found to be associated with hearing PC2 (P = 3.7×10(-8)) and further supported by whole-genome sequence in a subset.Our results suggest a developmental role of Sik3 in hearing and may be required for the maintenance of adult auditory function.

View Article: PubMed Central - PubMed

Affiliation: Department of Twin Research and Genetic Epidemiology, King's College London, London SE1 7EH, UK.

Show MeSH
Related in: MedlinePlus