A natural loss-of-function deletion of the cytohesin 1 (Cyth1) gene in BALB/cByJ mice does not impact cardiomyocyte polyploidy

Mammalian cardiomyocytes (CMs) mostly become polyploid shortly after birth. Because this feature may relate to several aspects of heart biology, including regeneration after injury, the mechanisms that cause polyploidy are of interest. BALB/cJ and BALB/cByJ mice are highly related sister strains that diverge substantially in CM ploidy. We identified a large deletion in the Cyth1 gene that arose uniquely in BALB/cByJ mice that creates a null allele. The deletion also results in ectopic transcription of the downstream gene Dnah17, although this transcript is unlikely to encode a protein. By evaluating the natural null allele from BALB/cByJ and an engineered knockout allele in the C57BL/6 background, we determined that absence of Cyth1 does not by itself influence CM ploidy. The ready availability of BALB/cByJ mice may be helpful to other investigations of Cyth1 in other biological processes. Bulk RNA-Seq from ventricles of BALB/cJ and BALB/cByJ neonatal (P4) mice. 3-4 hearts were pooled for each sample.哺乳动物心肌细胞（cardiomyocytes，简称CMs）大多在出生后短期内便进入多倍体状态。由于该特征与心脏生物学的多个维度相关，包括损伤后的再生能力，因此调控多倍体形成的分子机制成为研究热点。BALB/cJ与BALB/cByJ小鼠属于高度同源的姐妹品系，但二者的心肌细胞多倍体水平存在显著差异。本研究在BALB/cByJ小鼠中发现了Cyth1基因的特异性大片段缺失突变，该突变可产生一个无效等位基因（null allele）。该缺失同时会导致下游基因Dnah17发生异位转录，但该转录本大概率无法编码功能性蛋白质。本研究通过分析BALB/cByJ小鼠的天然无效等位基因，以及C57BL/6遗传背景下的工程化敲除等位基因，证实Cyth1基因的缺失本身并不会直接影响心肌细胞的多倍体状态。BALB/cByJ小鼠易于获取，可为其他探索Cyth1基因在不同生物学过程中功能的研究提供支持。本数据集包含BALB/cJ与BALB/cByJ新生（出生后第4天，P4）小鼠心室的批量RNA测序（bulk RNA-Seq）数据，每个样本混合3~4颗心脏。