title: Hearing Dysfunction inXpa-Deficient Mice.
abstract: Xeroderma pigmentosum (XP) is a rare recessive heredity disease caused by DNA repair impairment characterized by photosensitivity and neurologic symptoms in half of the cases. There are eight subtypes of XP: XP-A-XP-G and XP variant. Among eight subtypes, XP complementation group A (XP-A) display the lowest DNA repair ability and the severest cutaneous and neurologic symptoms. While its pathogenesis of skin symptoms have been well-studied, that of neurological symptoms, including sensorineural hearing loss (SNHL) remains unknown. Basic studies have suggested that SNHL may be caused by inner ear damage, including damage to the spiral ganglion neurons and organ of Corti, and that the XP-A is associated with most severe form of SNHL in humans. Here, we report the occurrence of SNHL inXpa-deficient mice.Xpa-deficient mice and wild-type mice underwent measurements for auditory brainstem response, and the results revealed thatXpa-deficient mice exhibited significantly greater (p< 0.01) ABR thresholds at 4, 8, and 16 kHz than the wild-type mice. Furthermore, the number of spiral ganglion neurons was reduced inXpa-deficient mice compared with that in wild-type mice, indicating that hearing loss may be related to spiral ganglion neuron deficiency, consistent with the few reports published in human patients with XP. These results provide important insights into the pathogenesis of SNHL in patients with XP-A.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Kobe University Graduate School of Medicine Kobe, Japan.
authors.forename: Hitomi
authors.initials: H
authors.lastname: Shinomiya
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Kobe University Graduate School of Medicine Kobe, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Yamashita
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Kobe University Graduate School of Medicine Kobe, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Fujita
authors.affiliation: Division of Dermatology, Department of Internal Related Graduate School of Medicine, Kobe University Kobe, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Nakano
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Kobe University Graduate School of Medicine Kobe, Japan.
authors.forename: Go
authors.initials: G
authors.lastname: Inokuchi
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Kobe University Graduate School of Medicine Kobe, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Hasegawa
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Kobe University Graduate School of Medicine Kobe, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Otsuki
authors.affiliation: Division of Dermatology, Department of Internal Related Graduate School of Medicine, Kobe University Kobe, Japan.
authors.forename: Chikako
authors.initials: C
authors.lastname: Nishigori
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Kobe University Graduate School of Medicine Kobe, Japan.
authors.forename: Ken-Ichi
authors.initials: KI
authors.lastname: Nibu
keywords: ABR; SNHL; XP; organ of Corti; spiral ganglion neuron; stria vascularis