Hereditary susceptibility to inner ear stress agents studied in heterozygotes of the German waltzing guinea pig
Author: Skjönsberg, Åsa
Date: 2006-09-22
Location: Föreläsningssalen, Rolf Lufts auditorium, Karolinska Universitetssjukhuset, Solna
Time: 09.00
Department: Institutionen för klinisk neurovetenskap / Department of Clinical Neuroscience
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Thesis (656.5Kb)
Abstract
The German waltzing guinea pig is a strain of animals expressing deafness and severe balance disorders already at birth. The mutation arose spontaneously in a breeding facility in Germany and as the affected animals show a characteristic waltzing behavior, the strain is named the German waltzing guinea pig. The strain is presently bred only at Karolinska Institutet.
The hereditary inner car impairment has a recessive mode of inheritance and the strain thus produces not only affected homozygotes but also symptom-free heterozygotes and fully normal offspring. The outcome depends solely on the genotype of the parents. The beterozygotes, which have obtained the "waltzing" gene from one parent only, have normal hearing and no balance dysfunction. The heterozygous animals appear normal but will, in turn, carry the genetic defect to the next generation. The present thesis is focused on these animals.
Noise and ototoxic drugs are well known stress factors that interfere negatively with the hearing organ in both humans and animals, causing hearing impairment. However, the inter-individual variability in susceptibility to auditory stress factors is surprisingly large, most likely due to different genetic predisposition. In this study heterozygous animals of the German waltzing guinea pig, animals carrying a genetic defect known to cause severe hearing impairment, were used to study how an unexplored gene for deafness interacts with the auditory stress agents; noise exposure and the ototoxic drugs gentamicin and cisplatin.
Animals were exposed to both narrowband as well as broadband noise at different ages and hearing threshold were conducted using ABR. Heterozygote animals of the German waltzing guinea pigs showed less threshold shifts compared to control strains. Old animals were less affected of the noise trauma than younger animals.
To explore the hypothesis that the efferent system contribute to the protection of the inner ear against noise trauma, measurements using the new methods of post onset adaptation of the DPOAE and maximum adaptation magnitude were used. The post onset adaptation of the DPOAE could detect a strain difference at the higher frequency region while in the maximum adaptation magnitude method showed no difference between the strains.
The heterozygous animals of the German waltzing guinea pig displayed a distinctly increased resistance to noise exposures, manifested as reduced threshold shifts and faster recovery following acoustic overstimulation. However, when exposed to ototoxic drugs, the heterozygous carriers suffered from a more pronounced hearing loss. It is concluded that endogenous resistance to noise in the heterozygotes does not offer any protection against ototoxic drugs. The detailed mechanisms still need to be explored.
The hereditary inner car impairment has a recessive mode of inheritance and the strain thus produces not only affected homozygotes but also symptom-free heterozygotes and fully normal offspring. The outcome depends solely on the genotype of the parents. The beterozygotes, which have obtained the "waltzing" gene from one parent only, have normal hearing and no balance dysfunction. The heterozygous animals appear normal but will, in turn, carry the genetic defect to the next generation. The present thesis is focused on these animals.
Noise and ototoxic drugs are well known stress factors that interfere negatively with the hearing organ in both humans and animals, causing hearing impairment. However, the inter-individual variability in susceptibility to auditory stress factors is surprisingly large, most likely due to different genetic predisposition. In this study heterozygous animals of the German waltzing guinea pig, animals carrying a genetic defect known to cause severe hearing impairment, were used to study how an unexplored gene for deafness interacts with the auditory stress agents; noise exposure and the ototoxic drugs gentamicin and cisplatin.
Animals were exposed to both narrowband as well as broadband noise at different ages and hearing threshold were conducted using ABR. Heterozygote animals of the German waltzing guinea pigs showed less threshold shifts compared to control strains. Old animals were less affected of the noise trauma than younger animals.
To explore the hypothesis that the efferent system contribute to the protection of the inner ear against noise trauma, measurements using the new methods of post onset adaptation of the DPOAE and maximum adaptation magnitude were used. The post onset adaptation of the DPOAE could detect a strain difference at the higher frequency region while in the maximum adaptation magnitude method showed no difference between the strains.
The heterozygous animals of the German waltzing guinea pig displayed a distinctly increased resistance to noise exposures, manifested as reduced threshold shifts and faster recovery following acoustic overstimulation. However, when exposed to ototoxic drugs, the heterozygous carriers suffered from a more pronounced hearing loss. It is concluded that endogenous resistance to noise in the heterozygotes does not offer any protection against ototoxic drugs. The detailed mechanisms still need to be explored.
List of papers:
I. Skjonsberg A, Herrlin P, Duan M, Johnson AC, Ulfendahl M (2005). A guinea pig strain with recessive heredity of deafness, producing normal-hearing heterozygotes with resistance to noise trauma. Audiol Neurootol. 10(6): 323-30.
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II. Halsey K, Skjonsberg A, Ulfendahl M, Dolan DF (2005). Efferent-mediated adaptation of the DPOAE as a predictor of aminoglycoside toxicity. Hear Res. 201(1-2): 99-108.
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III. Skjonsberg A, Halsey K, Ulfendahl M, Dolan DF (2006). Exploring efferent-mediated adaptation of the DPOAE in three different guinea pig strains. [Submitted]
IV. Skjonsberg A, Bucinskaite V, Laurell G, Ulfendahl M (2006). Augmented ototoxic effect of cisplatin in heterozygotes of the German waltzing guinea pig. [Submitted]
I. Skjonsberg A, Herrlin P, Duan M, Johnson AC, Ulfendahl M (2005). A guinea pig strain with recessive heredity of deafness, producing normal-hearing heterozygotes with resistance to noise trauma. Audiol Neurootol. 10(6): 323-30.
Fulltext (DOI)
Pubmed
View record in Web of Science®
II. Halsey K, Skjonsberg A, Ulfendahl M, Dolan DF (2005). Efferent-mediated adaptation of the DPOAE as a predictor of aminoglycoside toxicity. Hear Res. 201(1-2): 99-108.
Fulltext (DOI)
Pubmed
View record in Web of Science®
III. Skjonsberg A, Halsey K, Ulfendahl M, Dolan DF (2006). Exploring efferent-mediated adaptation of the DPOAE in three different guinea pig strains. [Submitted]
IV. Skjonsberg A, Bucinskaite V, Laurell G, Ulfendahl M (2006). Augmented ototoxic effect of cisplatin in heterozygotes of the German waltzing guinea pig. [Submitted]
Issue date: 2006-09-01
Rights:
Publication year: 2006
ISBN: 91-7140-817-7
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