遗传修饰猪模型在生物医学及农业领域研究进展及应用

doi:10.16288/j.yczz.22-313

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Hereditas(Beijing) ›› 2023, Vol. 45 ›› Issue (1): 6-28.doi: 10.16288/j.yczz.22-313

• Invited Review • Previous Articles Next Articles

Advances and applications of genetically modified pig models in biomedical and agricultural field

Fei Gao¹(), Yu Wang²(), Jiaxiang Du³(), Xuguang Du¹(), Jianguo Zhao²(), Dengke Pan⁴(), Sen Wu¹(), Yaofeng Zhao¹()

1. State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing 100193, China
2. Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China
3. Chengdu Clonorgan Biotechnology Co., Ltd, Chengdu 610000, China
4. Clinical Immunology Translational Medicine Key Laboratory of Sichuan Province, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, Chengdu 610072, China

Received:2022-10-08 Revised:2022-11-26 Online:2023-01-20 Published:2022-12-28
Contact: Du Xuguang,Zhao Jianguo,Pan Dengke,Wu Sen,Zhao Yaofeng E-mail:gaofei2020019@cau.edu.cn;wangyu950306@163.com;jxdu@clonorgan.com;xuguangdu@cau.edu.cn;zhaojg@ioz.ac.cn;pandengke2002@163.com;swu@cau.edu.cn;yaofengzhao@cau.edu.cn
Supported by:
Supported by the National Key Research and Development Program of China No(2021YFA0805900);Hainan Yazhou Bay Seed Laboratory No(B21HJ0103)

Abstract

Abstract:

Compared with rodents, pigs are closer to humans in terms of anatomy, metabolism and physiology, so they are ideal animal models of human diseases and xenotransplantation donors. In addition, as one of the most important livestock in China, pigs are closely related to our lives in terms of breeding improvement, disease prevention and animal welfare. In this review, we mainly summarize the research progress and future application of genetically modified pig models in the fields of xenotransplantation, molecular breeding and human disease models. We wish to take this opportunity to raise the awareness of researchers in related fields on cutting-edge technologies such as gene editing and understand the significance of genetically modified pig models in life science research.

Key words: genetically modified pig models, molecular breeding, disease models, xenotransplantation

Fei Gao, Yu Wang, Jiaxiang Du, Xuguang Du, Jianguo Zhao, Dengke Pan, Sen Wu, Yaofeng Zhao. Advances and applications of genetically modified pig models in biomedical and agricultural field[J]. Hereditas(Beijing), 2023, 45(1): 6-28.

Figures/Tables 7

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育种方向	靶基因	编辑类型	表型	参考文献
提高生产性能	MSTN	基因敲除	提高产肉量	[17~22]
	IGF2	突变ZBED6结合位点	提高产肉量	[26, 27]
	FBXO40	基因敲除	提高产肉量	[30]
	UCP1	基因插入	提高抗寒能力和瘦肉率	[32]
提高抗病力	CD163	基因敲除/片段缺失/同源替换	抵抗PRRSV	[38~45]
	APN	基因敲除	抵抗TGEV	[47]~49
	-	过表达shRNA	抵抗CSFV	[53,54]
优良性状聚合	CD163/APN	基因敲除	同时抵抗PRRSV和TGEV	[51]
优良性状聚合	CD163/MSTN/IGF2	基因敲除/基因过表达	提高产肉量同时抵抗PRRSV	[58]

人类疾病	基因	修饰方式	参考文献
阿尔兹海默症	APP695sw	敲入	[65]
	PSEN1^M146I	重组酶介导的盒式置换	[66]
	APP^SW、PSEN1^M146I	突变	[67]
	hAPP、hTau、hPS1	多顺反子介导的突变	[68]
亨廷顿舞蹈症	HTT	转基因	[69]
亨廷顿舞蹈症	HTT	定点敲入	[70]
帕金森综合征	Parkin、DJ-1	敲除	[71]
	PARK2、DJ-1、PINK1	敲除	[72]
	PARK2、PINK1	敲除	[73]
	SNCA	点突变	[74]
肌萎缩侧索硬化症	SOD1^G93A	转基因	[75]

人类疾病	基因	修饰方式	参考文献
囊性纤维化	CFTR	敲除	[76]
	CFTR	敲除	[77]
	CFTR	敲除和突变	[78,79]
杜氏肌营养不良	DMD	敲除	[80]
杜氏肌营养不良	DMD	敲除	[81]
哈钦森-吉尔福德早衰综合征	LMNA	点突变	[82]
酪氨酸血症	FAH	敲除	[83]
苯丙酮尿症	PAH	敲除	[84]
血友病B	hF9	敲入	[85]
血管性血友病	vWF	敲除	[86]

人类疾病	基因	修饰方式	参考文献
乳腺癌	BRCA1	敲除	[95]
结直肠癌	APC¹³¹¹、APC¹⁰¹⁶	点突变	[96]
胃癌	RUNX3	敲除	[97]
肺癌	EML4、ALK	敲入和重排	[98]
骨肉瘤	TP53	敲除	[99]
多种肿瘤	KRAS^G12D、TP53^R167H	点突变	[100]
淋巴瘤、肾母细胞瘤和骨源性肿瘤	TP53^R167H	点突变	[101]

人类疾病	基因	修饰方式	参考文献
人类永久性新生儿糖尿病	INS	点突变	[102]
糖尿病	INS	敲除	[103]
3型成熟型青年糖尿病	HGF1α	转基因	[104]
2型糖尿病	GIPR	转基因	[105]
	hIAPP	敲入	[106]
	11β-HSD1、HIAPP、CHOP	敲入	[107]
非酒精性脂肪肝	GIPR^dn、hIAPP、PNPLA3^I148M	定点敲入	[108]
高甘油三酯血症	ApoCIII	转基因	[109]
高胆固醇血症、自发动脉粥样硬化	PCSK9	转基因	[110]
高胆固醇血症、自发动脉粥样硬化	ApoE	敲除	[111]
高胆固醇血症、自发动脉粥样硬化、饮食诱导加速疾病发生	LDLR	敲除	[112]
血清LDL-C和TC水平升高	ApoE和LDLR	敲除	[113]
胆固醇吸收失调	NPC1L1	敲除	[114]

Advances and applications of genetically modified pig models in biomedical and agricultural field

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