Progressive hearing loss is very common in the human population but we know little about the underlying molecular mechanisms. Synaptojanin2 (Synj2) has been reported to be involved, as a mouse mutation led to a progressive increase in auditory thresholds with age. Synaptojanin2 is a phosphatidylinositol (PI) phosphatase that removes the five-position phosphates from phosphoinositides, such as PIP₂ and PIP₃, and is a key enzyme in clathrin-mediated endocytosis. To investigate the mechanisms underlying progressive hearing loss, we have studied a different mutation of mouse Synj2 to look for any evidence of involvement of vesicle trafficking particularly affecting the synapses of sensory hair cells. Auditory brainstem responses (ABR) developed normally at first but started to decline between 3 and 4 weeks of age in Synj2^tm1b mutants. At 6 weeks old, some evidence of outer hair cell (OHC) stereocilia fusion and degeneration was observed, but this was only seen in the extreme basal turn so cannot explain the raised ABR thresholds that correspond to more apical regions of the cochlear duct. We found no evidence of any defect in inner hair cell (IHC) exocytosis or endocytosis using single hair cell recordings, nor any sign of hair cell synaptic abnormalities. Endocochlear potentials (EP) were normal. The mechanism underlying progressive hearing loss in these mutants remains elusive, but our findings of raised distortion product otoacoustic emission (DPOAE) thresholds and signs of OHC degeneration both suggest an OHC origin for the hearing loss. Synaptojanin2 is not required for normal development of hearing but it is important for its maintenance.

进行性听力损失在人群中非常常见，但我们对其潜在的分子机制知之甚少。突触贾宁2 (合成2据报道，这与小鼠的突变有关，导致听觉阈值随着年龄的增长而逐渐增加。 Synaptojanin2 是一种磷脂酰肌醇 (PI) 磷酸酶，可去除磷酸肌醇（例如 PIP ₂和 PIP ₃ ）中的五位磷酸，是网格蛋白介导的内吞作用中的关键酶。为了研究进行性听力损失的机制，我们研究了小鼠的不同突变合成2寻找任何涉及囊泡运输的证据，特别是影响感觉毛细胞突触的证据。听觉脑干反应 (ABR) 最初发育正常，但在 3 至 4 周龄之间开始下降合成^{2 tm1b}突变体。在 6 周大时，观察到了外毛细胞 (OHC) 静纤毛融合和退化的一些证据，但这仅在极端基底转向中出现，因此无法解释与耳蜗管更多顶端区域相对应的 ABR 阈值升高。使用单毛细胞记录，我们没有发现内毛细胞 (IHC) 胞吐作用或内吞作用有任何缺陷的证据，也没有发现任何毛细胞突触异常的迹象。耳蜗内电位（EP）正常。这些突变体进行性听力损失的机制仍然难以捉摸，但我们对失真产物耳声发射 (DPOAE) 阈值升高和 OHC 变性迹象的发现都表明听力损失的 OHC 起源。 Synaptojanin2 不是听力正常发育所必需的，但对于听力的维持很重要。