title: Muscle developmental defects in heterogeneous nuclear Ribonucleoprotein A1 knockout mice.
abstract: 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 hnRNP A1 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 hnRNP A1+/-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.
authors.affiliation: Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, Republic of China.
authors.forename: Ting-Yuan
authors.initials: TY
authors.lastname: Liu
authors.affiliation: Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, Republic of China.
authors.forename: Yu-Chia
authors.initials: YC
authors.lastname: Chen
authors.affiliation: Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, Republic of China.|Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, Republic of China.|Departments of Pediatrics and Clinical Laboratory, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, Republic of China.|Department of Biological Science and Technology, Institute of Molecular Medicine and Bioengineering, College of Biological Science and Technology, National Chiao Tung University, Hsinchu, Taiwan, Republic of China.
authors.forename: Yuh-Jyh
authors.initials: YJ
authors.lastname: Jong
authors.affiliation: Institute of Biomedical Sciences, Mackay Medical College, New Taipei City, Taiwan, Republic of China.
authors.forename: Huai-Jen
authors.initials: HJ
authors.lastname: Tsai
authors.affiliation: Epigenome Research Center, China Medical University, Taichung, Taiwan, Republic of China.
authors.forename: Chien-Chin
authors.initials: CC
authors.lastname: Lee
authors.affiliation: Epigenome Research Center, China Medical University, Taichung, Taiwan, Republic of China.|Department of Laboratory Medicine, China Medical University, Taichung, Taiwan, Republic of China.|Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung, Taiwan, Republic of China.
authors.forename: Ya-Sian
authors.initials: YS
authors.lastname: Chang
authors.affiliation: Epigenome Research Center, China Medical University, Taichung, Taiwan, Republic of China d6781@mail.cmuh.org.tw.|Department of Laboratory Medicine, China Medical University, Taichung, Taiwan, Republic of China.|School of Medicine, China Medical University, Taichung, Taiwan, Republic of China.
authors.forename: Jan-Gowth
authors.initials: JG
authors.lastname: Chang
authors.affiliation: Department of Biomedical Science and Environmental Biology, College of Life Science, Kaohsiung Medical University, Kaohsiung, Taiwan, Republic of China m795003@kmu.edu.tw.
authors.forename: Yung-Fu
authors.identifier: 0000-0003-0917-4747
authors.initials: YF
authors.lastname: Chang
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D002448:Cell Adhesion; D004622:Embryo, Mammalian / Q000002:abnormalities / Q000503:physiopathology*; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D000076245:Heterogeneous Nuclear Ribonucleoprotein A1 / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D009119:Muscle Contraction; D024510:Muscle Development; D009124:Muscle Proteins / Q000235:genetics; D018482:Muscle, Skeletal / Q000002:abnormalities* / Q000196:embryology / Q000503:physiopathology; D017422:Sequence Analysis, DNA; D015854:Up-Regulation
chemical_list: D000076245:Heterogeneous Nuclear Ribonucleoprotein A1; C000619657:Hnrnpa1 protein, mouse; D009124:Muscle Proteins
keywords: alternative splicing; embryonic development; hnRNP A1; knockout mice; muscle development