扩张型心肌病动物模型及治疗的研究进展

doi:10.3785/j.issn.1008-9209.2023.05.081

浙江大学学报（农业与生命科学版）

2024, Vol. 50

Issue (1): 1-11 DOI: 10.3785/j.issn.1008-9209.2023.05.081

青年科学家论坛

扩张型心肌病动物模型及治疗的研究进展

金佳敏,巩倩,庄乐南(

)

浙江大学动物科学学院，浙江杭州 310058

Advances in animal models and treatment of dilated cardiomyopathy

Jiamin JIN,Qian GONG,Lenan ZHUANG(

)

College of Animal Sciences, Zhejiang University, Hangzhou 310058, Zhejiang, China

全文: PDF(940 KB) HTML

摘要：

扩张型心肌病（dilated cardiomyopathy, DCM）是一类以一侧或双侧心室扩张和收缩功能障碍为特征的心血管疾病，发病原因包括遗传性的基因突变及多种继发因素。人类DCM动物模型涉及小鼠、大鼠、斑马鱼、猪等多种实验动物，一般通过基因编辑、药物诱导、自身免疫缺陷诱导、病毒感染等方法构建。借助DCM动物模型，研究者对该病的致病机制和治疗靶点进行了深入的研究。本文简述了人类DCM的病理特征、临床症状和流行病学特征，对近年来DCM动物模型的种类和构建方法进行了综述，并对优化造模方法与推动治疗研究提出了新的展望。基于DCM动物模型的治疗研究可以帮助我们更好地理解DCM的发生机制，为开发新的治疗方法提供依据。

关键词： 扩张型心肌病; 疾病动物模型; 生物治疗; 基因编辑

Abstract:

Dilated cardiomyopathy (DCM) is a cardiovascular disease characterized by one or both ventricular dilation and systolic dysfunction. Its pathogenesis involves inherited genetic mutations and various secondary factors. Human DCM animal models have been developed using a variety of experimental animals such as mice, rats, zebrafish, and pigs, and are generally constructed by gene editing, drug induction, autoimmune deficiency induction, and viral infection. The previous studies have utilized DCM animal models to thoroughly investigate the pathogenic mechanisms and therapeutic targets of this disease. This paper briefly described the pathological features, clinical symptoms, and epidemiological characteristics of human DCM. Furthermore, it reviewed the types of DCM animal models and their construction methods used in recent years. This paper also presented new perspectives on optimizing modeling methods and promoting therapeutic research for DCM. Therapeutic studies based on DCM animal models can help us better understand the mechanisms of DCM and provide a basis for the development of new therapeutic approaches.

Key words: dilated cardiomyopathy animal models of disease biological therapy gene editing

收稿日期: 2023-05-08 出版日期: 2024-03-02

CLC:

S85

基金资助: 国家重点研发计划项目(2021YFA0805902);国家自然科学基金项目(32270884)

通讯作者: 庄乐南 E-mail: zhuangln@zju.edu.cn

作者简介: 金佳敏（https://orcid.org/0009-0006-8512-1865），E-mail：3190101400@zju.edu.cn|庄乐南，浙江大学动物科学学院“百人计划”研究员，博士生导师。2011 年博士毕业于中国科学院上海生物化学与细胞生物学研究所，于2013 年赴美国国立卫生研究院（NIH）糖尿病、消化和肾脏疾病研究所（NIDDK）从事表观遗传与代谢疾病相关研究，2018年赴美国得克萨斯大学西南医学中心（UTSW）从事表观遗传与肌肉、心脏疾病相关研究。目前担任浙江大学动物科学学院动物医学系副主任，Life、Medicine、Journal of Veterinary and Marine Research 等多本学术期刊的编委或学术编辑，中国畜牧兽医学会动物生理生化学分会及动物遗传育种学分会理事。主要研究方向为利用基因编辑猪模型研究心血管代谢与疾病的表观遗传学与转录调控机制。主持国家自然科学基金项目2项，国家重点研发计划课题1 项，浙江大学校长专项前沿基础研究计划1 项，在Nature、Circulation、Nature Communications、Biomaterials、The Journal of Clinical Investigation、PNAS等国际高水平期刊上发表学术论文30 余篇。（https://orcid.org/0000-0001-9561-8396），E-mail：zhuangln@zju.edu.cn.

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引用本文:

金佳敏,巩倩,庄乐南. 扩张型心肌病动物模型及治疗的研究进展[J]. 浙江大学学报（农业与生命科学版）, 2024, 50(1): 1-11.

Jiamin JIN,Qian GONG,Lenan ZHUANG. Advances in animal models and treatment of dilated cardiomyopathy. Journal of Zhejiang University (Agriculture and Life Sciences), 2024, 50(1): 1-11.

链接本文:

https://www.zjujournals.com/agr/CN/10.3785/j.issn.1008-9209.2023.05.081 或 https://www.zjujournals.com/agr/CN/Y2024/V50/I1/1

图1 DCM动物模型

表1 基因编辑DCM动物模型的细胞类型和生物体

图2 DCM的3种治疗途径

34	JIN B, SHI H M, ZHU J, et al. Up-regulating autophagy by targeting the mTOR-4EBP1 pathway: a possible mechanism for improving cardiac function in mice with experimental dilated cardiomyopathy[J]. BMC Cardiovascular Disorders, 2020, 20: 56. DOI: 10.1186/s12872-020-01365-9 doi: 10.1186/s12872-020-01365-9
35	WU J, SUN P, CHEN Q, et al. Metabolic reprogramming orchestrates CD4+ T-cell immunological status and restores cardiac dysfunction in autoimmune induced-dilated cardiomyo-pathy mice[J]. Journal of Molecular and Cellular Cardiology, 2019, 135: 134-148. DOI: 10.1016/j.yjmcc.2019.08.002 doi: 10.1016/j.yjmcc.2019.08.002
36	KONG Q, GU J P, LU R H, et al. NMR-based metabolomic analysis of cardiac tissues clarifies molecular mechanisms of CVB3-induced viral myocarditis and dilated cardiomyopathy[J]. Molecules, 2022, 27(18): 6115. DOI: 10.3390/molecules27186115 doi: 10.3390/molecules27186115
37	ZHANG Y, ZHOU X B, CHEN S Y, et al. Immune mechanisms of group B coxsackievirus induced viral myocarditis[J]. Virulence, 2023, 14(1): 2180951. DOI: 10.1080/21505594.2023.2180951 doi: 10.1080/21505594.2023.2180951
38	ZHAO Y R, LI H P, DU H Z, et al. A Kaposi’s sarcoma-associated herpes virus-encoded microRNA contributes to dilated cardiomyopathy[J]. Signal Transduction and Targeted Therapy, 2023, 8: 226. DOI: 10.1038/s41392-023-01434-3 doi: 10.1038/s41392-023-01434-3
39	PIEDALLU O, DEVOS P, MOUGENOT N, et al. AAV-driven human BAG3 overexpression unexpectedly exacerbate heart failure in a LMNAH222P DCM mice model[J]. Archives of Cardiovascular Diseases Supplements, 2022, 14(2): 192. DOI: 10.1016/j.acvdsp.2022.04.082 doi: 10.1016/j.acvdsp.2022.04.082
40	ZHANG C, ZHOU Y, LAI X, et al. Human umbilical cord mesenchymal stem cells alleviate myocardial endothelial-mesenchymal transition in a rat dilated cardiomyopathy model[J]. Transplantation Proceedings, 2019, 51(3): 936-941. DOI: 10.1016/j.transproceed.2019.01.080 doi: 10.1016/j.transproceed.2019.01.080
41	CHEN Q Q, ZENG Y, YANG X L, et al. Resveratrol ameliorates myocardial fibrosis by regulating Sirt1/Smad3 deacetylation pathway in rat model with dilated cardiomyo-pathy[J]. BMC Cardiovascular Disorders, 2022, 22: 17. DOI: 10.1186/s12872-021-02401-y doi: 10.1186/s12872-021-02401-y
42	DOS SANTOS COUTINHO E SILVA R, ZANONI F L, SIMAS R, et al. Effect of bilateral sympathectomy in a rat model of dilated cardiomyopathy induced by doxorubicin[J]. The Journal of Thoracic and Cardiovascular Surgery, 2020, 160(3): e135-e144. DOI: 10.1016/j.jtcvs.2019.09.031 doi: 10.1016/j.jtcvs.2019.09.031
43	PANG X F, LIN X, DU J J, et al. LTBP2 knockdown by siRNA reverses myocardial oxidative stress injury, fibrosis and remodelling during dilated cardiomyopathy[J]. Acta Physiologica, 2020, 228(3): e13377. DOI: 10.1111/apha.13377 doi: 10.1111/apha.13377
1	RAMPERSAUD E, KINNAMON D D, HAMILTON K, et al. Common susceptibility variants examined for association with dilated cardiomyopathy[J]. Annals of Human Genetics, 2010, 74(2): 110-116. DOI: 10.1111/j.1469-1809.2010.00566.x doi: 10.1111/j.1469-1809.2010.00566.x
2	WERNER S, WALLUKAT G, BECKER N P, et al. The aptamer BC 007 for treatment of dilated cardiomyopathy: evaluation in Doberman pinschers of efficacy and outcomes[J]. ESC Heart Failure, 2020, 7(3): 844-855. DOI: 10.1002/ehf2.12628 doi: 10.1002/ehf2.12628
44	DIOFANO F, WEINMANN K, SCHNEIDER I, et al. Genetic compensation prevents myopathy and heart failure in an in vivo model of Bag3 deficiency[J]. PLoS Genetics, 2020, 16(11): e1009088. DOI: 10.1371/journal.pgen.1009088 doi: 10.1371/journal.pgen.1009088
45	KAMEL S M, VAN OPBERGEN C J M, KOOPMAN C D, et al. Istaroxime treatment ameliorates calcium dysregulation in a zebrafish model of phospholamban R14del cardiomyopathy[J]. Nature Communications, 2021, 12: 7151. DOI: 10.1038/s41467-021-27461-8 doi: 10.1038/s41467-021-27461-8
46	TRUJILLO A S, HSU K H, PUTHAWALA J, et al. Myosin dilated cardiomyopathy mutation S532P disrupts actomyosin interactions, leading to altered muscle kinetics, reduced locomotion, and cardiac dilation in Drosophila [J]. Molecular Biology of the Cell, 2021, 32(18): 1690-1706. DOI: 10.1091/mbc.E21-02-0088 doi: 10.1091/mbc.E21-02-0088
47	PETERSEN C E, WOLF M J, SMYTH J T. Suppression of store-operated calcium entry causes dilated cardiomyopathy of the Drosophila heart[J]. Biology Open, 2020, 9(3): bio049999. DOI: 10.1242/bio.049999 doi: 10.1242/bio.049999
48	STEPHENS E H, TIMEK T A, DAUGHTERS G T, et al. Significant changes in mitral valve leaflet matrix composition and turnover with tachycardia-induced cardiomyopathy[J]. Circulation, 2009, 120(): S112-S119. DOI: 10.1161/CIRCULATIONAHA.108.844159 doi: 10.1161/CIRCULATIONAHA.108.844159
49	ISHIKAWA K. Experimental Models of Cardiovascular Diseases: Methods and Protocols[M]. New York: Springer New York, 2018. DOI: 10.1007/978-1-4939-8597-5 doi: 10.1007/978-1-4939-8597-5
50	SCHNEIDER J W, OOMMEN S, QURESHI M Y, et al. Dysregulated ribonucleoprotein granules promote cardiomyo-pathy in RBM20 gene-edited pigs[J]. Nature Medicine, 2020, 26(11): 1788-1800. DOI: 10.1038/s41591-020-1087-x doi: 10.1038/s41591-020-1087-x
51	TALAVERA J, GIRALDO A, FERNÁNDEZ-DEL-PALACIO M J, et al. An upgrade on the rabbit model of anthracycline-induced cardiomyopathy: shorter protocol, reduced mortality, and higher incidence of overt dilated cardiomyopathy[J]. BioMed Research International, 2015, 2015: 465342. DOI: 10.1155/2015/465342 doi: 10.1155/2015/465342
52	HARE J M, FISHMAN J E, GERSTENBLITH G, et al. Comparison of allogeneic vs autologous bone marrow-derived mesenchymal stem cells delivered by transendocardial injection in patients with ischemic cardiomyopathy: the POSEIDON randomized trial[J]. JAMA, 2012, 308(22): 2369-2379. DOI: 10.1001/jama.2012.25321 doi: 10.1001/jama.2012.25321
53	BAN K W, PARK H J, KIM S S, et al. Cell therapy with embryonic stem cell-derived cardiomyocytes encapsulated in injectable nanomatrix gel enhances cell engraftment and promotes cardiac repair[J]. ACS Nano, 2014, 8(10): 10815-10825. DOI: 10.1021/nn504617g doi: 10.1021/nn504617g
54	KOUDSTAAL S, JANSEN OF LORKEERS S J, GAETANI R, et al. Concise review: heart regeneration and the role of cardiac stem cells[J]. Stem Cells Translational Medicine, 2013, 2(6): 434-443. DOI: 10.5966/sctm.2013-0001 doi: 10.5966/sctm.2013-0001
55	HIRAI K, OUSAKA D, FUKUSHIMA Y, et al. Cardiosphere-derived exosomal microRNAs for myocardial repair in pediatric dilated cardiomyopathy[J]. Science Translational Medicine, 2020, 12(573): eabb3336. DOI: 10.1126/scitranslmed.abb3336 doi: 10.1126/scitranslmed.abb3336
56	GROSCH M, SCHRAFT L, CHAN A, et al. Striated muscle-specific base editing enables correction of mutations causing dilated cardiomyopathy[J]. Nature Communications, 2023, 14: 3714. DOI: 10.1038/s41467-023-39352-1 doi: 10.1038/s41467-023-39352-1
57	WEINTRAUB R G, SEMSARIAN C, MACDONALD P. Dilated cardiomyopathy[J]. The Lancet, 2017, 390(10092): 400-414. DOI: 10.1016/S0140-6736(16)31713-5 doi: 10.1016/S0140-6736(16)31713-5
58	WESS G, WALLUKAT G, FRITSCHER A, et al. Doberman pinschers present autoimmunity associated with functional autoantibodies: a model to study the autoimmune background of human dilated cardiomyopathy[J]. PLoS ONE, 2019, 14(7): e0214263. DOI: 10.1371/journal.pone.0214263 doi: 10.1371/journal.pone.0214263
59	HENLEY M J, KOEHLER A N. Advances in targeting ‘undruggable’ transcription factors with small molecules[J]. Nature Reviews Drug Discovery, 2021, 20(9): 669-688. DOI: 10.1038/s41573-021-00199-0 doi: 10.1038/s41573-021-00199-0
60	PANG S, DONG W, LIU N, et al. Diallyl sulfide protects against dilated cardiomyopathy via inhibition of oxidative stress and apoptosis in mice[J]. Molecular Medicine Reports, 2021, 24(6): 852. DOI: 10.3892/mmr.2021.12492 doi: 10.3892/mmr.2021.12492
61	YEREBAKAN C, BOLTZE J, ELMONTASER H, et al. Effects of pulmonary artery banding in doxorubicin-induced left ventricular cardiomyopathy[J]. The Journal of Thoracic and Cardiovascular Surgery, 2019, 157(6): 2416-2428.e4. DOI: 10.1016/j.jtcvs.2019.01.138 doi: 10.1016/j.jtcvs.2019.01.138
62	ISAKA M, HAYASHIDA R, TAMASHIMA Y, et al. Surgical ventricular restoration for rabbit dilated cardiomyopathy model: preliminary study[J]. Research in Veterinary Science, 2021, 136: 373-376. DOI: 10.1016/j.rvsc.2021.03.023 doi: 10.1016/j.rvsc.2021.03.023
63	MOHIUDDIN M M, SINGH A K, SCOBIE L, et al. Graft dysfunction in compassionate use of genetically engineered pig-to-human cardiac xenotransplantation: a case report[J]. The Lancet, 2023, 402(10399):397-410. DOI: 10.1016/S0140-6736(23)00775-4 doi: 10.1016/S0140-6736(23)00775-4
3	HEINEKE J, WOLLERT K C, OSINSKA H, et al. Calcineurin protects the heart in a murine model of dilated cardiomyopathy[J]. Journal of Molecular and Cellular Cardiology, 2010, 48(6): 1080-1087. DOI: 10.1016/j.yjmcc.2009.10.012 doi: 10.1016/j.yjmcc.2009.10.012
4	张百会,侯煜,陈晓春.扩张型心肌病的病因和发病机理的研究进展[J].中西医结合心血管病电子杂志,2016,4(28):17-18. DOI:10.16282/j.cnki.cn11-9336/r.2016.28.011 ZHANG B H, HOU Y, CHEN X C. Advances in the etiology and pathogenesis of dilated cardiomyopathy[J]. Cardiovascular Disease Electronic Journal of Integrated Traditional Chinese and Western Medicine, 2016, 4(28): 17-18. (in Chinese) doi: 10.16282/j.cnki.cn11-9336/r.2016.28.011
5	MØLLER D V, ANDERSEN P S, HEDLEY P, et al. The role of sarcomere gene mutations in patients with idiopathic dilated cardiomyopathy[J]. European Journal of Human Genetics, 2009, 17(10): 1241-1249. DOI: 10.1038/ejhg.2009.34 doi: 10.1038/ejhg.2009.34
6	聂宏运,刘小玲,张佳伟,等.扩张型心肌病致病基因及基因多态性研究进展[J].国际心血管病杂志,2022,49(3):129-132. DOI:10.3969/j.issn.1673-6583.2022.03.001 NIE H Y, LIU X L, ZHANG J W, et al. Research progress of pathogenic genes and gene polymorphismsin dilated cardiomyo-pathy[J]. International Journal of Cardiovascular Disease, 2022, 49(3): 129-132. (in Chinese) doi: 10.3969/j.issn.1673-6583.2022.03.001
7	EHSAN M, JIANG H, L.THOMSON K, et al. When signalling goes wrong: pathogenic variants in structural and signalling proteins causing cardiomyopathies[J]. Journal of Muscle Research and Cell Motility, 2017, 38(3/4): 303-316. DOI: 10.1007/s10974-017-9487-3 doi: 10.1007/s10974-017-9487-3
8	CIARAMBINO T, MENNA G, SANSONE G, et al. Cardio-myopathies: an overview[J]. International Journal of Molecular Sciences, 2021, 22(14): 7722. DOI: 10.3390/ijms22147722 doi: 10.3390/ijms22147722
9	YANG L Z, SUN J H, CHEN Z, et al. The Lmna p.R541C mutation causes dilated cardiomyopathy in human and mice[J]. International Journal of Cardiology, 2022, 363: 149-158. DOI: 10.1016/j.ijcard.2022.06.038 doi: 10.1016/j.ijcard.2022.06.038
10	HOMBURGER F, BAKER J R, NIXON C W, et al. New hereditary disease of Syrian hamsters: primary, generalized polymyopathy and cardiac necrosis[J]. Archives of Internal Medicine, 1962, 110(5): 660-662.
11	马宝霞,沈文璐,王旭,等.基因编辑动物模型在人类疾病研究中的应用[J].生物工程学报,2020,36(5):849-860. DOI:10.13345/j.cjb.190395 MA B X, SHEN W L, WANG X, et al. Gene edited animal models applied in human disease research[J]. Chinese Journal of Biotechnology, 2020, 36(5): 849-860. (in Chinese with English abstract) doi: 10.13345/j.cjb.190395
12	REICHART D, LINDBERG E L, MAATZ H, et al. Pathogenic variants damage cell composition and single cell transcription in cardiomyopathies[J]. Science, 2022, 377(6606): eabo1984. DOI: 10.1126/science.abo1984 doi: 10.1126/science.abo1984
13	CHAFFIN M, PAPANGELI I, SIMONSON B, et al. Single-nucleus profiling of human dilated and hypertrophic cardio-myopathy[J]. Nature, 2022, 608(7921): 174-180. DOI: 10.1038/s41586-022-04817-8 doi: 10.1038/s41586-022-04817-8
14	CHUN Y W, MIYAMOTO M, WILLIAMS C H, et al. Impaired reorganization of centrosome structure underlies human infantile dilated cardiomyopathy[J]. Circulation, 2023, 147(17): 1291-1303. DOI: 10.1161/CIRCULATIONAHA.122.060985 doi: 10.1161/CIRCULATIONAHA.122.060985
15	MCLENDON J M, ZHANG X M, MATASIC D S, et al. Knockout of sorbin and SH3 domain containing 2 (Sorbs2) in cardiomyocytes leads to dilated cardiomyopathy in mice[J]. Journal of the American Heart Association, 2022, 11(13): e025687. DOI: 10.1161/JAHA.122.025687 doi: 10.1161/JAHA.122.025687
16	DOMÍNGUEZ F, LALAGUNA L, MARTÍNEZ-MARTÍN I, et al. Titin missense variants as a cause of familial dilated cardiomyopathy[J]. Circulation, 2023, 147(22): 1711-1713. DOI: 10.1161/CIRCULATIONAHA.122.062833 doi: 10.1161/CIRCULATIONAHA.122.062833
17	XIONG Y, BEDI K, BERRITT S, et al. Targeting MRTF/SRF in CAP2-dependent dilated cardiomyopathy delays disease onset[J]. JCI Insight, 2019, 4(6): e124629. DOI: 10.1172/jci.insight.124629 doi: 10.1172/jci.insight.124629
18	CHO E J, KANG H J, KANG D K, et al. Myocardial-specific ablation of Jumonji and AT-rich interaction domain-containing 2 (Jarid2) leads to dilated cardiomyopathy in mice[J]. The Journal of Biological Chemistry, 2019, 294(13): 4981-4996. DOI: 10.1074/jbc.RA118.005634 doi: 10.1074/jbc.RA118.005634
19	FENG Y L, CAI L Y, HONG W Z, et al. Rewiring of 3D chromatin topology orchestrates transcriptional reprogramming and the development of human dilated cardiomyopathy[J]. Circulation, 2022, 145(22): 1663-1683. DOI: 10.1161/CIRCULATIONAHA.121.055781 doi: 10.1161/CIRCULATIONAHA.121.055781
20	CHIMOSKEY J E, SPIELMAN W S, BRANDT M A, et al. Cardiac atria of BIO 14.6 hamsters are deficient in natriuretic factor[J]. Science, 1984, 223(4638): 820-822.
21	BLAIN A M, STRAUB V W. δ-sarcoglycan-deficient muscular dystrophy: from discovery to therapeutic approaches[J]. Skeletal Muscle, 2011, 1(1): 13. DOI: 10.1186/2044-5040-1-13 doi: 10.1186/2044-5040-1-13
22	LIU C Z, SPINOZZI S, FENG W, et al. Homozygous G650del nexilin variant causes cardiomyopathy in mice[J]. JCI Insight, 2020, 5(16): e138780. DOI: 10.1172/jci.insight.138780 doi: 10.1172/jci.insight.138780
23	MIYAO N, HATA Y, IZUMI H, et al. TBX5 R264K acts as a modifier to develop dilated cardiomyopathy in mice indepen-dently of T-box pathway[J]. PLoS ONE, 2020, 15(4): e0227393. DOI: 10.1371/journal.pone.0227393 doi: 10.1371/journal.pone.0227393
24	YANG J, GRAFTON F, RANJBARVAZIRI S, et al. Phenotypic screening with deep learning identifies HDAC6 inhibitors as cardioprotective in a BAG3 mouse model of dilated cardiomyopathy[J]. Science Translational Medicine, 2022, 14(652): eabl5654. DOI: 10.1126/scitranslmed.abl5654 doi: 10.1126/scitranslmed.abl5654
25	POWERS J D, KIRKLAND N J, LIU C Z, et al. Subcellular remodeling in filamin C deficient mouse hearts impairs myocyte tension development during progression of dilated cardiomyopathy[J]. International Journal of Molecular Sciences, 2022, 23(2): 871. DOI: 10.3390/ijms23020871 doi: 10.3390/ijms23020871
26	YUN H H, JUNG S Y, PARK B W, et al. An adult mouse model of dilated cardiomyopathy caused by inducible cardiac-specific Bis deletion[J]. International Journal of Molecular Sciences, 2021, 22(3): 1343. DOI: 10.3390/ijms22031343 doi: 10.3390/ijms22031343
27	SPINOZZI S, LIU C Z, CHEN Z E, et al. Nexilin is necessary for maintaining the transverse-axial tubular system in adult cardiomyocytes[J]. Circulation Heart Failure, 2020, 13(7): e006935. DOI: 10.1161/CIRCHEARTFAILURE.120.006935 doi: 10.1161/CIRCHEARTFAILURE.120.006935
28	ANGELINI A, GOREY M A, DUMONT F, et al. Cardio-protective effects of α-cardiac actin on oxidative stress in a dilated cardiomyopathy mouse model[J]. The FASEB Journal, 2020, 34(2): 2987-3005. DOI: 10.1096/fj.201902389R doi: 10.1096/fj.201902389R
29	GAMMONS J, TREBAK M, MANCARELLA S. Cardiac-specific deletion of Orai3 leads to severe dilated cardiomyo-pathy and heart failure in mice[J]. Journal of the American Heart Association, 2021, 10(8): e019486. DOI: 10.1161/JAHA.120.019486 doi: 10.1161/JAHA.120.019486
30	TANNOUS C, DELOUX R, KAROUI A, et al. Nmrk2 gene is upregulated in dilated cardiomyopathy and required for cardiac function and NAD levels during aging[J]. Inter-national Journal of Molecular Sciences, 2021, 22(7): 3534. DOI: 10.3390/ijms22073534 doi: 10.3390/ijms22073534
31	LIU Y H, ZHANG W F, HU T T, et al. A doxorubicin-induced murine model of dilated cardiomyopathy in vivo [J]. Journal of Visualized Experiments, 2020(159): e61158. DOI: 10.3791/61158 doi: 10.3791/61158
32	LIU Y F, JIANG B, CAO Y D, et al. High expression levels and localization of Sox5 in dilated cardiomyopathy[J]. Molecular Medicine Reports, 2020, 22(2): 948-956. DOI: 10.3892/mmr.2020.11180 doi: 10.3892/mmr.2020.11180

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[2]	舒心媛, 严旭, 蒲烨弘, 王超, 潘建伟. CRISPR/Cas系统的作用原理及其在作物遗传改良中的应用[J]. 浙江大学学报（农业与生命科学版）, 2018, 44(3): 259-268.
[3]	王少华, 赵盼盼, 刘通, 丁彪, 罗磊, 曹祖兵, 张运海, 张坤. 利用CRISPR/Cas9n技术生产抗蓝耳病的基因编辑克隆猪[J]. 浙江大学学报（农业与生命科学版）, 2018, 44(2): 157-161.

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