title: Impaired auditory-vestibular functions and behavioral abnormalities of Slitrk6-deficient mice.
abstract: A recent study revealed that Slitrk6, a transmembrane protein containing a leucine-rich repeat domain, has a critical role in the development of the inner ear neural circuit. However, it is still unknown how the absence of Slitrk6 affects auditory and vestibular functions. In addition, the role of Slitrk6 in regions of the central nervous system, including the dorsal thalamus, has not been addressed. To understand the physiological role of Slitrk6, Slitrk6-knockout (KO) mice were subjected to systematic behavioral analyses including auditory and vestibular function tests. Compared to wild-type mice, the auditory brainstem response (ABR) of Slitrk6-KO mice indicated a mid-frequency range (8-16 kHz) hearing loss and reduction of the first ABR wave. The auditory startle response was also reduced. A vestibulo-ocular reflex (VOR) test showed decreased vertical (head movement-induced) VOR gains and normal horizontal VOR. In an open field test, locomotor activity was reduced; the tendency to be in the center region was increased, but only in the first 5 min of the test, indicating altered adaptive responses to a novel environment. Altered adaptive responses were also found in a hole-board test in which head-dip behavior was increased and advanced. Aside from these abnormalities, no clear abnormalities were noted in the mood, anxiety, learning, spatial memory, or fear memory-related behavioral tests. These results indicate that the Slitrk6-KO mouse can serve as a model of hereditary sensorineural deafness. Furthermore, the altered responses of Slitrk6-KO mice to the novel environment suggest a role of Slitrk6 in some cognitive functions.
authors.affiliation: Laboratory for Behavioral and Developmental Disorders, RIKEN Brain Science Institute, Wako-shi, Japan.
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Matsumoto
authors.forename: Kei-ichi
authors.initials: K
authors.lastname: Katayama
authors.forename: Takehito
authors.initials: T
authors.lastname: Okamoto
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Yamada
authors.forename: Noriko
authors.initials: N
authors.lastname: Takashima
authors.forename: Soichi
authors.initials: S
authors.lastname: Nagao
authors.forename: Jun
authors.initials: J
authors.lastname: Aruga
mesh_terms: D000818:Animals; D016057:Evoked Potentials, Auditory, Brain Stem; D034381:Hearing Loss; D008565:Membrane Proteins / Q000172:deficiency* / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity; D012027:Reflex, Vestibulo-Ocular; D014724:Vestibular Function Tests
chemical_list: D008565:Membrane Proteins; C488353:Slitrk6 protein, mouse