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ILDR1 deficiency causes degeneration of cochlear outer hair cells and disrupts the structure of the organ of Corti: a mouse model for human DFNB42.

Sang Q, Li W, Xu Y, Qu R, Xu Z, Feng R, Jin L, He L, Li H, Wang L - Biol Open (2015)

Bottom Line: ILDR1 deficiency affects expression of tricellulin in vivo, and this provides a possible explanation to hearing loss.Gene ontology classification indicated that a number of differentially expressed proteins are involved in cell adhesion, protein and vesicle-mediated transport, cell death, membrane organization, and cellular homeostasis.A few of these proteins are closely related to hearing development.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, 200032, PR China Institute of Biomedical Sciences, Fudan University, No 138 Yixueyuan Road, Shanghai, 200032, PR China.

No MeSH data available.


Related in: MedlinePlus

Hematoxylin and eosin labeling of frozen cochlear sections showing the structure of the organ of Corti.The organ of Corti from the apical (A–D), middle (E–H), and basal turns (I–L) of the cochlea are shown separately. Black arrows in J show the disruption of the organ of Corti in the basal turn of P15 Ildr1−/− mice. Black arrows in G,K show the progressive disruption of the organ of Corti in the basal and middle turns of P21 Ildr1−/− mice. Black arrows in D,H,L show the complete disruption of the organ of Corti in all turns of the cochleae of P28 Ildr1−/− mice.
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f06: Hematoxylin and eosin labeling of frozen cochlear sections showing the structure of the organ of Corti.The organ of Corti from the apical (A–D), middle (E–H), and basal turns (I–L) of the cochlea are shown separately. Black arrows in J show the disruption of the organ of Corti in the basal turn of P15 Ildr1−/− mice. Black arrows in G,K show the progressive disruption of the organ of Corti in the basal and middle turns of P21 Ildr1−/− mice. Black arrows in D,H,L show the complete disruption of the organ of Corti in all turns of the cochleae of P28 Ildr1−/− mice.

Mentions: To explore the underlying cause of hearing impairment, the morphologies of OHCs, IHCs, and the organs of Corti were examined at different postnatal developmental stages. Confocal microscopy, scanning electron microscopy, and immunohistochemistry revealed that OHCs, IHCs, supporting cells, and the organs of Corti developed normally and no difference in morphology was seen between P7 Ildr1−/− mice and P7 Ildr1+/− mice (supplementary material Figs S1 and S2). However, by P15 different degrees of OHC degeneration were observed in the basal, middle, and apical turns of the organ of Corti and approximately 60% of the outer hair cells in the whole cochlea were lost (Fig. 4B,F,J,M). By P21, the degree of OHC degeneration in the three turns of the organ of Corti was more severe than at P15. At P21, no OHCs were seen in the basal turns, there were almost no OHCs left in the middle turns, and only a few OHCs were seen in the apical turns (Fig. 4C,G,K,M). By P28, there were no OHCs visible in any of the turns of the organ of Corti (Fig. 4D,H,L). The immunofluorescence results were confirmed by scanning electron microscopy examination of the morphology of the basilar membrane from P15, P21, and P28 Ildr1+/− and Ildr1+/− mice (Fig. 5). In addition, hematoxylin and eosin staining showed that from P15 the structure and morphology of the organ of Corti was partly disrupted in the basal turn due to the loss of OHCs (Fig. 6J). The basal and middle turns of the organ of Corti were even more disrupted at P21 (Fig. 6C,G,K). At P28, the organ of Corti was completely disrupted throughout the entire cochlea and this resulted in the disappearance of the tunnel of the organ of Corti (Fig. 6D,H,L). Although OHCs and the organ of Corti showed abnormalities during early postnatal development, IHCs in Ildr1−/− mice remained intact throughout the observation period (Figs 4 and 5).


ILDR1 deficiency causes degeneration of cochlear outer hair cells and disrupts the structure of the organ of Corti: a mouse model for human DFNB42.

Sang Q, Li W, Xu Y, Qu R, Xu Z, Feng R, Jin L, He L, Li H, Wang L - Biol Open (2015)

Hematoxylin and eosin labeling of frozen cochlear sections showing the structure of the organ of Corti.The organ of Corti from the apical (A–D), middle (E–H), and basal turns (I–L) of the cochlea are shown separately. Black arrows in J show the disruption of the organ of Corti in the basal turn of P15 Ildr1−/− mice. Black arrows in G,K show the progressive disruption of the organ of Corti in the basal and middle turns of P21 Ildr1−/− mice. Black arrows in D,H,L show the complete disruption of the organ of Corti in all turns of the cochleae of P28 Ildr1−/− mice.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
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getmorefigures.php?uid=PMC4400585&req=5

f06: Hematoxylin and eosin labeling of frozen cochlear sections showing the structure of the organ of Corti.The organ of Corti from the apical (A–D), middle (E–H), and basal turns (I–L) of the cochlea are shown separately. Black arrows in J show the disruption of the organ of Corti in the basal turn of P15 Ildr1−/− mice. Black arrows in G,K show the progressive disruption of the organ of Corti in the basal and middle turns of P21 Ildr1−/− mice. Black arrows in D,H,L show the complete disruption of the organ of Corti in all turns of the cochleae of P28 Ildr1−/− mice.
Mentions: To explore the underlying cause of hearing impairment, the morphologies of OHCs, IHCs, and the organs of Corti were examined at different postnatal developmental stages. Confocal microscopy, scanning electron microscopy, and immunohistochemistry revealed that OHCs, IHCs, supporting cells, and the organs of Corti developed normally and no difference in morphology was seen between P7 Ildr1−/− mice and P7 Ildr1+/− mice (supplementary material Figs S1 and S2). However, by P15 different degrees of OHC degeneration were observed in the basal, middle, and apical turns of the organ of Corti and approximately 60% of the outer hair cells in the whole cochlea were lost (Fig. 4B,F,J,M). By P21, the degree of OHC degeneration in the three turns of the organ of Corti was more severe than at P15. At P21, no OHCs were seen in the basal turns, there were almost no OHCs left in the middle turns, and only a few OHCs were seen in the apical turns (Fig. 4C,G,K,M). By P28, there were no OHCs visible in any of the turns of the organ of Corti (Fig. 4D,H,L). The immunofluorescence results were confirmed by scanning electron microscopy examination of the morphology of the basilar membrane from P15, P21, and P28 Ildr1+/− and Ildr1+/− mice (Fig. 5). In addition, hematoxylin and eosin staining showed that from P15 the structure and morphology of the organ of Corti was partly disrupted in the basal turn due to the loss of OHCs (Fig. 6J). The basal and middle turns of the organ of Corti were even more disrupted at P21 (Fig. 6C,G,K). At P28, the organ of Corti was completely disrupted throughout the entire cochlea and this resulted in the disappearance of the tunnel of the organ of Corti (Fig. 6D,H,L). Although OHCs and the organ of Corti showed abnormalities during early postnatal development, IHCs in Ildr1−/− mice remained intact throughout the observation period (Figs 4 and 5).

Bottom Line: ILDR1 deficiency affects expression of tricellulin in vivo, and this provides a possible explanation to hearing loss.Gene ontology classification indicated that a number of differentially expressed proteins are involved in cell adhesion, protein and vesicle-mediated transport, cell death, membrane organization, and cellular homeostasis.A few of these proteins are closely related to hearing development.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, 200032, PR China Institute of Biomedical Sciences, Fudan University, No 138 Yixueyuan Road, Shanghai, 200032, PR China.

No MeSH data available.


Related in: MedlinePlus