A spontaneously arising, loss-of-function mutation in the RNA binding motif protein 20 (Rbm20) gene, which encodes a nuclear splicing protein, was previously identified as the underlying reason for expression of an abnormally large TITIN (TTN) protein in a rat model of cardiomyopathy. An outbreak of Pseudomonas aeruginosa led to submission of rats with dyspnea, sneezing, lethargy, nasal discharge, and/or unexpected death for diagnostic evaluation. Necropsy revealed underlying megaesophagus in Rbm20-/- rats. Further phenotyping of this rat strain and determination of the size of esophageal TTN was undertaken. The Rbm20-defective rats developed megaesophagus at an early age (26 weeks) with high frequency (13/32, 41%). They also often exhibited secondary rhinitis (9/32, 28%), aspiration pneumonia (8/32, 25%), and otitis media/interna (6/32, 19%). In addition, these rats had a high prevalence of hydronephrosis (13/32, 41%). RBM20 is involved in splicing multiple RNA transcripts, one of which is the muscle-specific protein TTN. Rbm20 mutations are a significant cause of dilated cardiomyopathy in humans. In Rbm20-defective rats, TTN size was significantly increased in the skeletal muscle of the esophagus. Megaesophagus in this rat strain (maintained on a mixed genetic background) is hypothesized to result from altered TTN stretch signaling in esophageal skeletal muscle. This study describes a novel mechanism for the development of megaesophagus, which may be useful for understanding the pathogenesis of megaesophagus in humans and offers insights into potential myogenic causes of this condition. This is the first report of megaesophagus and other noncardiac pathogenic changes associated with mutation of Rbm20 in any species.

中文翻译：

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大食管是大鼠Rbm20基因大量缺失的主要病理状况。

先前已确定编码核剪接蛋白的RNA结合基序蛋白20（Rbm20）基因中自发出现的功能丧失突变是大鼠中异常大TITIN（TTN）蛋白表达的根本原因心肌病模型。铜绿假单胞菌的暴发导致大鼠呼吸困难，打喷嚏，嗜睡，流鼻涕和/或意外死亡，以进行诊断评估。尸检显示Rbm20-/-大鼠中存在潜在的食管。对该大鼠品系进行进一步的表型分析并确定食道TTN的大小。Rbm20缺陷大鼠在早期（26周）以高频率（13 / 32，41％）发展为食管。他们还经常表现出继发性鼻炎（9/32，28％），吸入性肺炎（8/32，25％）和中耳/内耳炎（6/32，19％）。此外，这些大鼠肾盂积水的患病率很高（13 / 32，41％）。RBM20参与剪接多个RNA转录物，其中之一是肌肉特异性蛋白TTN。Rbm20突变是人类扩张型心肌病的重要原因。在Rbm20缺陷大鼠中，食道骨骼肌中TTN的大小显着增加。假定该大鼠品系中的食道（保持在混合的遗传背景下）是由于食管骨骼肌中TTN伸展信号的改变所致。这项研究描述了食管发展的一种新机制，这可能有助于了解人类食管的发病机理，并为这种情况的潜在成肌原因提供了见识。