Decreased cochlear DNA receptor staining in MRL.MpJ-Faslpr autoimmune mice with hearing loss

David M. Kaylie, Steven Hefeneider, J. Beth Kempton, Don C. Siess, Colleen T. Vedder, Louise S. Merkens, Dennis Trune

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Objectives: Previous studies of decreased cochlear DNA binding in autoimmune mice suggested that antibodies against a cochlear cell surface DNA receptor cause autoimmune hearing loss. However, the presence of a cochlear DNA receptor has not been determined. Therefore, immunohistochemistry with an anti-DNA receptor antibody was performed on MRL.MpJ-Faslpr (MRL/lpr) autoimmune mice to determine 1) which inner ear structures contain DNA receptors and 2) whether the receptor staining pattern changes as autoimmune disease progresses and hearing thresholds increase. Study Design: A prospective study of the progression of hearing loss in autoimmune mice and correlated alterations in immunostaining for the inner ear DNA receptor. Methods: One group of MRL/lpr mice (n = 10) was allowed to develop autoimmune disease, and auditory brainstem response (ABR) audiometry was performed at 4, 6, and 9 months of age to measure the progression of hearing loss. A second group (n = 5) was tested for ABR thresholds at 2 months of age and immediately killed to assess receptor staining before the onset of autoimmune disease and hearing loss. The inner ears from all mice were immunohistochemically stained with an anti-DNA receptor antibody, and a qualitative analysis of the staining of cochlear structures was performed. Results: Auditory brainstem response audiometry revealed a significant 20- to 30-dB elevation of thresholds as systemic disease progressed. Anti-DNA receptor staining was heaviest in the spiral ligament and less intense in the spiral ganglion and cochlear nerve. Both groups showed a similar pattern of staining in these structures. The stria vascularis and hair cells also stained in both groups. However, the stria cells of normal-hearing mice showed diffuse intracellular immunoreactivity, whereas older mice displayed less staining that was confined to the cell membranes. Conclusions: The inner ears of MRL/lpr mice contain DNA receptors. Autoimmune hearing loss was correlated with weaker overall intracellular staining in the stria vascularis and hair cells but increased staining of the cell membranes. This suggested DNA receptors have impaired endocytosis and more receptors remain on the cell membrane, possibly as a result of binding by circulating autoantibodies.

Original languageEnglish (US)
Pages (from-to)1275-1280
Number of pages6
JournalLaryngoscope
Volume111
Issue number7
StatePublished - 2001

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Cochlea
Hearing Loss
Staining and Labeling
Inbred MRL lpr Mouse
Inner Ear
Brain Stem Auditory Evoked Potentials
Stria Vascularis
Autoimmune Diseases
Audiometry
Antinuclear Antibodies
Cell Membrane
Hearing
Spiral Ligament of Cochlea
Spiral Ganglion
DNA receptor
Cochlear Nerve
Cell Surface Receptors
Endocytosis
Autoantibodies
Immunohistochemistry

Keywords

  • Autoimmune hearing loss
  • DNA receptor
  • Inner ear
  • MRL.MpJ-Fas mouse
  • Systemic lupus erythematosus

ASJC Scopus subject areas

  • Otorhinolaryngology

Cite this

Kaylie, D. M., Hefeneider, S., Kempton, J. B., Siess, D. C., Vedder, C. T., Merkens, L. S., & Trune, D. (2001). Decreased cochlear DNA receptor staining in MRL.MpJ-Faslpr autoimmune mice with hearing loss. Laryngoscope, 111(7), 1275-1280.

Decreased cochlear DNA receptor staining in MRL.MpJ-Faslpr autoimmune mice with hearing loss. / Kaylie, David M.; Hefeneider, Steven; Kempton, J. Beth; Siess, Don C.; Vedder, Colleen T.; Merkens, Louise S.; Trune, Dennis.

In: Laryngoscope, Vol. 111, No. 7, 2001, p. 1275-1280.

Research output: Contribution to journalArticle

Kaylie, DM, Hefeneider, S, Kempton, JB, Siess, DC, Vedder, CT, Merkens, LS & Trune, D 2001, 'Decreased cochlear DNA receptor staining in MRL.MpJ-Faslpr autoimmune mice with hearing loss', Laryngoscope, vol. 111, no. 7, pp. 1275-1280.
Kaylie DM, Hefeneider S, Kempton JB, Siess DC, Vedder CT, Merkens LS et al. Decreased cochlear DNA receptor staining in MRL.MpJ-Faslpr autoimmune mice with hearing loss. Laryngoscope. 2001;111(7):1275-1280.
Kaylie, David M. ; Hefeneider, Steven ; Kempton, J. Beth ; Siess, Don C. ; Vedder, Colleen T. ; Merkens, Louise S. ; Trune, Dennis. / Decreased cochlear DNA receptor staining in MRL.MpJ-Faslpr autoimmune mice with hearing loss. In: Laryngoscope. 2001 ; Vol. 111, No. 7. pp. 1275-1280.
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abstract = "Objectives: Previous studies of decreased cochlear DNA binding in autoimmune mice suggested that antibodies against a cochlear cell surface DNA receptor cause autoimmune hearing loss. However, the presence of a cochlear DNA receptor has not been determined. Therefore, immunohistochemistry with an anti-DNA receptor antibody was performed on MRL.MpJ-Faslpr (MRL/lpr) autoimmune mice to determine 1) which inner ear structures contain DNA receptors and 2) whether the receptor staining pattern changes as autoimmune disease progresses and hearing thresholds increase. Study Design: A prospective study of the progression of hearing loss in autoimmune mice and correlated alterations in immunostaining for the inner ear DNA receptor. Methods: One group of MRL/lpr mice (n = 10) was allowed to develop autoimmune disease, and auditory brainstem response (ABR) audiometry was performed at 4, 6, and 9 months of age to measure the progression of hearing loss. A second group (n = 5) was tested for ABR thresholds at 2 months of age and immediately killed to assess receptor staining before the onset of autoimmune disease and hearing loss. The inner ears from all mice were immunohistochemically stained with an anti-DNA receptor antibody, and a qualitative analysis of the staining of cochlear structures was performed. Results: Auditory brainstem response audiometry revealed a significant 20- to 30-dB elevation of thresholds as systemic disease progressed. Anti-DNA receptor staining was heaviest in the spiral ligament and less intense in the spiral ganglion and cochlear nerve. Both groups showed a similar pattern of staining in these structures. The stria vascularis and hair cells also stained in both groups. However, the stria cells of normal-hearing mice showed diffuse intracellular immunoreactivity, whereas older mice displayed less staining that was confined to the cell membranes. Conclusions: The inner ears of MRL/lpr mice contain DNA receptors. Autoimmune hearing loss was correlated with weaker overall intracellular staining in the stria vascularis and hair cells but increased staining of the cell membranes. This suggested DNA receptors have impaired endocytosis and more receptors remain on the cell membrane, possibly as a result of binding by circulating autoantibodies.",
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AU - Siess, Don C.

AU - Vedder, Colleen T.

AU - Merkens, Louise S.

AU - Trune, Dennis

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N2 - Objectives: Previous studies of decreased cochlear DNA binding in autoimmune mice suggested that antibodies against a cochlear cell surface DNA receptor cause autoimmune hearing loss. However, the presence of a cochlear DNA receptor has not been determined. Therefore, immunohistochemistry with an anti-DNA receptor antibody was performed on MRL.MpJ-Faslpr (MRL/lpr) autoimmune mice to determine 1) which inner ear structures contain DNA receptors and 2) whether the receptor staining pattern changes as autoimmune disease progresses and hearing thresholds increase. Study Design: A prospective study of the progression of hearing loss in autoimmune mice and correlated alterations in immunostaining for the inner ear DNA receptor. Methods: One group of MRL/lpr mice (n = 10) was allowed to develop autoimmune disease, and auditory brainstem response (ABR) audiometry was performed at 4, 6, and 9 months of age to measure the progression of hearing loss. A second group (n = 5) was tested for ABR thresholds at 2 months of age and immediately killed to assess receptor staining before the onset of autoimmune disease and hearing loss. The inner ears from all mice were immunohistochemically stained with an anti-DNA receptor antibody, and a qualitative analysis of the staining of cochlear structures was performed. Results: Auditory brainstem response audiometry revealed a significant 20- to 30-dB elevation of thresholds as systemic disease progressed. Anti-DNA receptor staining was heaviest in the spiral ligament and less intense in the spiral ganglion and cochlear nerve. Both groups showed a similar pattern of staining in these structures. The stria vascularis and hair cells also stained in both groups. However, the stria cells of normal-hearing mice showed diffuse intracellular immunoreactivity, whereas older mice displayed less staining that was confined to the cell membranes. Conclusions: The inner ears of MRL/lpr mice contain DNA receptors. Autoimmune hearing loss was correlated with weaker overall intracellular staining in the stria vascularis and hair cells but increased staining of the cell membranes. This suggested DNA receptors have impaired endocytosis and more receptors remain on the cell membrane, possibly as a result of binding by circulating autoantibodies.

AB - Objectives: Previous studies of decreased cochlear DNA binding in autoimmune mice suggested that antibodies against a cochlear cell surface DNA receptor cause autoimmune hearing loss. However, the presence of a cochlear DNA receptor has not been determined. Therefore, immunohistochemistry with an anti-DNA receptor antibody was performed on MRL.MpJ-Faslpr (MRL/lpr) autoimmune mice to determine 1) which inner ear structures contain DNA receptors and 2) whether the receptor staining pattern changes as autoimmune disease progresses and hearing thresholds increase. Study Design: A prospective study of the progression of hearing loss in autoimmune mice and correlated alterations in immunostaining for the inner ear DNA receptor. Methods: One group of MRL/lpr mice (n = 10) was allowed to develop autoimmune disease, and auditory brainstem response (ABR) audiometry was performed at 4, 6, and 9 months of age to measure the progression of hearing loss. A second group (n = 5) was tested for ABR thresholds at 2 months of age and immediately killed to assess receptor staining before the onset of autoimmune disease and hearing loss. The inner ears from all mice were immunohistochemically stained with an anti-DNA receptor antibody, and a qualitative analysis of the staining of cochlear structures was performed. Results: Auditory brainstem response audiometry revealed a significant 20- to 30-dB elevation of thresholds as systemic disease progressed. Anti-DNA receptor staining was heaviest in the spiral ligament and less intense in the spiral ganglion and cochlear nerve. Both groups showed a similar pattern of staining in these structures. The stria vascularis and hair cells also stained in both groups. However, the stria cells of normal-hearing mice showed diffuse intracellular immunoreactivity, whereas older mice displayed less staining that was confined to the cell membranes. Conclusions: The inner ears of MRL/lpr mice contain DNA receptors. Autoimmune hearing loss was correlated with weaker overall intracellular staining in the stria vascularis and hair cells but increased staining of the cell membranes. This suggested DNA receptors have impaired endocytosis and more receptors remain on the cell membrane, possibly as a result of binding by circulating autoantibodies.

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KW - DNA receptor

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KW - MRL.MpJ-Fas mouse

KW - Systemic lupus erythematosus

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