Kresge Hearing Research Institute, University of Michigan, Ann Arbor, MI 48109, USA.
Hear Res. 2011 Dec;282(1-2):63-8. doi: 10.1016/j.heares.2011.09.004. Epub 2011 Oct 1.
The membrane glycoprotein CTL2/SLC44A2 is expressed by supporting cells in the inner ear and has been identified as a target of antibodies that may induce auto-immune hearing loss. To determine if CTL2/SLC44A2 also has roles in inner ear development and to distinguish between isoform-specific roles, we assessed age-related changes in expression of CTL2/SLC44A2 isoforms and protein in the developing murine inner ear. We determined that both isoform p1 and isoform p2 (named for the upstream p1 and proximal p2 promoters that control alternate exons 1a and 1b) were robustly expressed as early as E14 and persisted during embryonic development, but after birth the p1 isoform fell to barely detectable levels while isoform p2 levels were maintained. This trend continued and became even more apparent later in post-natal development and remained in mature ears until at least 6 weeks of age. In aged (18 mo old) mice, the level of isoform p1 transcripts rose again to levels similar to the p2 isoform like that seen early in development. At the earliest stage examined, CTL2/SLC44A2 protein was expressed in both immature supporting cells and immature sensory cells, but after birth expression in the sensory cells declined in both the utricle and cochlea and by day P1 expression of CTL2/SLC44A2 was restricted to supporting cells. The changes we observed in isoform distribution are indicative of differential developmental roles and age related changes between the two isoforms of CTL2/SLC44A2 in the inner ear.
CTL2/SLC44A2 是一种膜糖蛋白，在内耳的支持细胞中表达，已被鉴定为可能诱导自身免疫性听力损失的抗体的靶标。为了确定 CTL2/SLC44A2 是否也在内耳发育中起作用，并区分同工型特异性作用，我们评估了发育中小鼠内耳中 CTL2/SLC44A2 同工型和蛋白的年龄相关变化。我们确定，同工型 p1 和同工型 p2（分别命名为控制交替外显子 1a 和 1b 的上游 p1 和近端 p2 启动子）在 E14 时就强烈表达，并在胚胎发育过程中持续表达，但出生后 p1 同工型降至几乎无法检测到的水平，而同工型 p2 水平保持不变。这种趋势持续存在，在出生后发育后期变得更加明显，并在成熟耳朵中至少持续到 6 周龄。在老年（18 月龄）小鼠中，同工型 p1 转录本的水平再次升高到与发育早期相似的 p2 同工型水平。在我们检查的最早阶段，CTL2/SLC44A2 蛋白在未成熟的支持细胞和未成熟的感觉细胞中均有表达，但出生后，感觉细胞在耳石和耳蜗中的表达均下降，并且在 P1 时 CTL2/SLC44A2 的表达仅限于支持细胞。我们观察到的同工型分布变化表明 CTL2/SLC44A2 的两种同工型在内耳中的发育作用和年龄相关变化不同。
