title: Mice doubly deficient in the midkine and pleiotrophin genes exhibit deficits in the expression of beta-tectorin gene and in auditory response.
abstract: alpha-Tectorin and beta-tectorin are major noncollagenous proteins of the tectorial membrane, which plays a crucial role in the reception of sonic signals in the cochlea. Midkine and pleiotrophin are closely related proteins that serve as growth factors and cytokines. In mice doubly deficient in the midkine gene and pleiotrophin gene, expression of beta-tectorin mRNA was nearly abolished in the cochlea on day 1 and 7 after birth. Expression of alpha-tectorin mRNA was unaffected in the double knockout mice, and expression of beta-tectorin mRNA was not altered in mice deficient in only the midkine or pleiotrophin gene. In newborn wild-type mice, both midkine and pleiotrophin were expressed in the greater epithelial ridge of the cochlea, in which beta-tectorin mRNA was strongly expressed. These results indicate that either midkine or pleiotrophin is required for significant expression of beta-tectorin. In agreement with the view that beta-tectorin is essential for normal auditory function, mice doubly deficient in both midkine and pleiotrophin genes exhibited very severe auditory deficits. We observed that mice deficient in either midkine or pleiotrophin gene were also impaired in their auditory response, but the level of the deficit was generally low or moderate. The present finding illustrates the importance of growth factor expression in the cochlea for auditory function.
authors.affiliation: Department of Biochemistry, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Japan.
authors.forename: Peng
authors.initials: P
authors.lastname: Zou
authors.forename: Hisako
authors.initials: H
authors.lastname: Muramatsu
authors.forename: Michihiko
authors.initials: M
authors.lastname: Sone
authors.forename: Hideo
authors.initials: H
authors.lastname: Hayashi
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Nakashima
authors.forename: Takashi
authors.initials: T
authors.lastname: Muramatsu
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001309:Auditory Threshold / Q000502:physiology; D002352:Carrier Proteins / Q000235:genetics; D016207:Cytokines / Q000172:deficiency* / Q000235:genetics; D016057:Evoked Potentials, Auditory, Brain Stem / Q000502:physiology; D016326:Extracellular Matrix Proteins; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D006309:Hearing / Q000502:physiology*; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D018345:Mice, Knockout; D000078792:Midkine; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013680:Tectorial Membrane / Q000737:chemistry / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D016207:Cytokines; D016326:Extracellular Matrix Proteins; D008565:Membrane Proteins; D012333:RNA, Messenger; C512625:beta-tectorin, mouse; C066845:pleiotrophin; D000078792:Midkine