標題: Muscle developmental defects in heterogeneous nuclear Ribonucleoprotein A1 knockout mice
作者: Liu, Ting-Yuan
Chen, Yu-Chia
Jong, Yuh-Jyh
Tsai, Huai-Jen
Lee, Chien-Chin
Chang, Ya-Sian
Chang, Jan-Gowth
Chang, Yung-Fu
生物資訊研究所
Institude of Bioinformatics
關鍵字: alternative splicing;embryonic development;hnRNP A1;knockout mice;musde development
公開日期: 1-Jan-2017
摘要: Heterogeneous ribonucleoprotein A1 (hnRNP A1) is crucial for regulating alternative splicing. Its integrated function within an organism has not, however, been identified. We generated hnRNP A1 knockout mice to study the role of hnRNPA1 in vivo. The knockout mice, hnRNP A1(-/-), showed embryonic lethality because of muscle developmental defects. The blood pressure and heart rate of the heterozygous mice were higher than those of the wild-type mice, indicating heart function defects. We performed mouse exon arrays to study the muscle development mechanism. The processes regulated by hnRNP A1 included cell adhesion and muscle contraction. The expression levels of muscle development-related genes in hnRNPA1(+/-) mice were significantly different from those in wild-type mice, as detected using qRT-PCR. We further confirmed the alternative splicing patterns of muscle development-related genes including mef2c, lrrfip1, usp28 and abcc9. Alternative mRNA isoforms of these genes were increased in hnRNP A1(+/-) mice compared with wild-type mice. Furthermore, we revealed that the functionally similar hnRNP A2/B1 did not compensate for the expression of hnRNP A1 in organisms. In summary, our study demonstrated that hnRNP A1 plays a critical and irreplaceable role in embryonic muscle development by regulating the expression and alternative splicing of muscle-related genes.
URI: http://dx.doi.org/10.1098/rsob.160303
http://hdl.handle.net/11536/133327
ISSN: 2046-2441
DOI: 10.1098/rsob.160303
期刊: OPEN BIOLOGY
Volume: 7
Issue: 1
起始頁: 0
結束頁: 0
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