Wolfson Centre for Age-Related Diseases, King's College London, London, United Kingdom.
Wellcome Sanger Institute, Hinxton, United Kingdom.
PLoS One. 2022 Mar 2;17(3):e0261530. doi: 10.1371/journal.pone.0261530. eCollection 2022.
Tasmanian devil (tde) mice are deaf and exhibit circling behaviour. Sensory hair cells of mutants show disorganised hair bundles with abnormally thin stereocilia. The origin of this mutation is the insertion of a transgene which disrupts expression of the Grxcr1 (glutaredoxin cysteine rich 1) gene. We report here that Grxcr1 exons and transcript sequences are not affected by the transgene insertion in tde homozygous (tde/tde) mice. Furthermore, 5'RACE PCR experiments showed the presence of two different transcripts of the Grxcr1 gene, expressed in both tde/tde and in wild-type controls. However, quantitative analysis of Grxcr1 transcripts revealed a significantly decreased mRNA level in tde/tde mice. The key stereociliary proteins ESPN, MYO7A, EPS8 and PTPRQ were distributed in hair bundles of homozygous tde mutants in a similar pattern compared with control mice. We found that the abnormal morphology of the stereociliary bundle was associated with a reduction in the size and Ca2+-sensitivity of the mechanoelectrical transducer (MET) current. We propose that GRXCR1 is key for the normal growth of the stereociliary bundle prior to the onset of hearing, and in its absence hair cells are unable to mature into fully functional sensory receptors.
塔斯马尼亚恶魔（tde）小鼠耳聋，并表现出转圈行为。突变体的感觉毛细胞显示出毛发束排列紊乱，静纤毛异常变薄。这种突变的起源是插入一个转基因，破坏了 Grxcr1（谷氧还蛋白富含半胱氨酸 1）基因的表达。我们在这里报告，Grxcr1 外显子和转录本序列不受 tde 纯合子（tde/tde）小鼠中转基因插入的影响。此外，5'RACE PCR 实验表明，Grxcr1 基因存在两种不同的转录本，在 tde/tde 和野生型对照中均有表达。然而，Grxcr1 转录本的定量分析显示，tde/tde 小鼠的 mRNA 水平显著降低。关键的静纤毛蛋白 ESPN、MYO7A、EPS8 和 PTPRQ 在纯合 tde 突变体的毛束中分布与对照小鼠相似。我们发现，静纤毛束的异常形态与机械电换能器（MET）电流的大小和 Ca2+敏感性降低有关。我们提出，GRXCR1 是在听力出现之前，静纤毛束正常生长所必需的，在其缺失的情况下，毛细胞无法成熟为完全功能的感觉受体。
