Zou Peng, Muramatsu Hisako, Sone Michihiko, Hayashi Hideo, Nakashima Tsutomu, Muramatsu Takashi
Department of Biochemistry, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Japan.
Lab Invest. 2006 Jul;86(7):645-53. doi: 10.1038/labinvest.3700428. Epub 2006 Apr 17.
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.
α - 耳盖蛋白和β - 耳盖蛋白是盖膜的主要非胶原蛋白，盖膜在耳蜗声音信号的接收中起关键作用。中期因子和多效生长因子是密切相关的蛋白质，可作为生长因子和细胞因子。在中期因子基因和多效生长因子基因双敲除的小鼠中，出生后第1天和第7天，耳蜗中β - 耳盖蛋白mRNA的表达几乎完全消失。α - 耳盖蛋白mRNA的表达在双敲除小鼠中未受影响，并且在仅缺失中期因子或多效生长因子基因的小鼠中，β - 耳盖蛋白mRNA的表达也未改变。在新生野生型小鼠中，中期因子和多效生长因子均在耳蜗的大上皮嵴中表达，其中β - 耳盖蛋白mRNA强烈表达。这些结果表明，中期因子或多效生长因子是β - 耳盖蛋白显著表达所必需的。与β - 耳盖蛋白对正常听觉功能至关重要的观点一致，中期因子和多效生长因子基因双敲除的小鼠表现出非常严重的听觉缺陷。我们观察到，仅缺失中期因子或多效生长因子基因的小鼠在听觉反应方面也有受损，但缺陷程度通常较低或中等。目前的发现说明了耳蜗中生长因子表达对听觉功能的重要性。
