神经母细胞瘤动物模型研究进展与应用

doi:10.12300/j.issn.1674-5817.2022.194

实验动物与比较医学 ›› 2023, Vol. 43 ›› Issue (3): 288-296.DOI: 10.12300/j.issn.1674-5817.2022.194

神经母细胞瘤动物模型研究进展与应用

谭志刚¹^,²(), 刘锦信¹^,², 郑楚雅¹^,², 廖文峰¹^,², 冯露平¹^,², 彭红丽¹^,², 严秀³, 卓振建¹^,²()()

^1.北京大学深圳研究生院实验动物中心, 深圳 518055
^2.省部共建肿瘤化学基因组学国家重点实验室, 深圳 518055
^3.佛山科学技术学院, 佛山 528200

收稿日期:2022-12-29 修回日期:2023-04-11 出版日期:2023-06-25 发布日期:2023-07-18
通讯作者: 卓振建（1990—），男，博士，副研究员，主要从事肿瘤模型构建、实验动物管理、肿瘤机制研究。E-mail： zhenjianzhuo@163.com。ORCID： 0000-0003-0142-4086
作者简介:谭志刚（1989—），男，硕士，兽医师，主要从事实验动物设施管理、实验动物疾病研究等。E-mail： 18819267200@163.com
基金资助:
国家自然科学基金项目“遗传变异调控ALKBH5基因表达影响神经母细胞瘤迁移侵袭的作用及机制研究”(82002636);深圳市自然科学基金项目“N1－甲基腺苷修饰基因与神经母细胞瘤遗传易感的机制研究”(JCYJ20220531093213030)

Advances and Applications in Animal Models of Neuroblastoma

Zhigang TAN¹^,²(), Jinxin LIU¹^,², Chuya ZHENG¹^,², Wenfeng LIAO¹^,², Luping FENG¹^,², Hongli PENG¹^,², Xiu YAN³, Zhenjian ZHUO¹^,²()()

^1.Laboratory Animal Center, Peking University Shenzhen Graduate School, Shenzhen 518055, China
^2.State Key Laboratory of Chemical Oncogenomics, Shenzhen 518055, China
^3.Foshan University, Foshan 528200, China

Received:2022-12-29 Revised:2023-04-11 Published:2023-06-25 Online:2023-07-18
Contact: ZHUO Zhenjian (ORCID: 0000-0003-0142-4086), E-mail: zhenjianzhuo@163.com

摘要/Abstract

摘要：

神经母细胞瘤（neuroblastoma，NB）是儿童最常见的实体恶性肿瘤，居我国儿童肿瘤发病率第四位，占儿童肿瘤死亡人数的15%，高危患者存活率低。目前对于NB的发病及药物治疗机制知之甚少。NB动物模型可以表征NB发展特征，是研究预防和治疗NB的重要工具，然而尚未有一种动物模型可以模拟人类NB的所有特征。本文介绍了当前研究较多的几种NB动物模型（小鼠模型、鸡胚绒毛尿囊膜模型和斑马鱼模型），并对每种NB动物模型的种类、构建方法、特征、优缺点及研究进展做了详细阐述，同时对NB的应用方向及前景进行概括，以期为NB动物模型构建和NB治疗等提供理论依据。

关键词: 神经母细胞瘤, 动物模型, 小鼠, 鸡胚绒毛尿囊膜, 斑马鱼

Abstract:

Neuroblastoma (NB) is one of the most common malignant solid tumors in children, ranks fourth in the incidence of pediatric tumors, and accounts for 15% of pediatric tumor deaths in children in China. Despite the development of new treatment options, the prognosis for high-risk patients is still poor. An animal model that can replicate the tumorigenesis of NB is an important tool for the prevention and treatment of NB. However, there are currently no animal models that can simulate all features of human NB. To provide a reference for the construction of animal models and treatment of NB, this article introduced several animal models of NB that have been extensively researched: the mouse, chick embryo chorioallantoic membrane, and zebrafish models. At the same time, it elaborated on the species, construction methods, characteristics, advantages and disadvantages, and research progress in NB.

Key words: Neuroblastoma, Animal model, Mice, Chick embryo chorioallantoic-membrane, Zebrafish

中图分类号:

R-332

谭志刚, 刘锦信, 郑楚雅, 廖文峰, 冯露平, 彭红丽, 严秀, 卓振建. 神经母细胞瘤动物模型研究进展与应用[J]. 实验动物与比较医学, 2023, 43(3): 288-296.

Zhigang TAN, Jinxin LIU, Chuya ZHENG, Wenfeng LIAO, Luping FENG, Hongli PENG, Xiu YAN, Zhenjian ZHUO. Advances and Applications in Animal Models of Neuroblastoma[J]. Laboratory Animal and Comparative Medicine, 2023, 43(3): 288-296.

图/表 3

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细胞系 Cell line	小鼠品系 Mouse stain	MYCN基因状态 MYCN status	ALK基因突变 ALK mutation	P53基因突变 P53 mutation	参考文献 Reference
KELLY	BALB/c-nude小鼠	扩增	野生型	野生型	[11]
CHP-212	NSG小鼠	扩增	野生型	野生型	[12]
SKNAS	BALB/c-nude小鼠	非扩增	野生型	H168R	[13]
SH-SY-5Y	Foxn1nu/Nju小鼠、ICR小鼠、BALB/c-nude小鼠	非扩增	F1174L	野生型	[14-16]
IMR-32	NSG小鼠	扩增	野生型	野生型	[17]
IMR-05	SHC小鼠	扩增	野生型	野生型	[18]
LA-N-5	BALB/c-nude小鼠	扩增	R1275Q	野生型	[19]
NB-1	BALB/c-nude小鼠	扩增	野生型扩增	野生型	[20-21]
SK-N-BE(2)	SCID-Beige小鼠	扩增	野生型	C135F	[10]
SK-N-BE(2)-C	BALB/c- nude小鼠、Foxn1nu/Nju小鼠	扩增	野生型	C135F	[11, 22]
CHP-134	NOD-SCID小鼠	扩增	野生型	野生型	[23]
SK-N-DZ	BALB/c-nude小鼠	扩增	野生型	R110L	[24]

细胞系 Cell line	小鼠品系 Mouse stain	MYCN基因状态 MYCN status	ALK基因突变 ALK mutation	P53基因突变 P53 mutation	参考文献 Reference
KELLY	BALB/c-nude小鼠	扩增	野生型	野生型	[11]
CHP-212	NSG小鼠	扩增	野生型	野生型	[12]
SKNAS	BALB/c-nude小鼠	非扩增	野生型	H168R	[13]
SH-SY-5Y	Foxn1nu/Nju小鼠、ICR小鼠、BALB/c-nude小鼠	非扩增	F1174L	野生型	[14-16]
IMR-32	NSG小鼠	扩增	野生型	野生型	[17]
IMR-05	SHC小鼠	扩增	野生型	野生型	[18]
LA-N-5	BALB/c-nude小鼠	扩增	R1275Q	野生型	[19]
NB-1	BALB/c-nude小鼠	扩增	野生型扩增	野生型	[20-21]
SK-N-BE(2)	SCID-Beige小鼠	扩增	野生型	C135F	[10]
SK-N-BE(2)-C	BALB/c- nude小鼠、Foxn1nu/Nju小鼠	扩增	野生型	C135F	[11, 22]
CHP-134	NOD-SCID小鼠	扩增	野生型	野生型	[23]
SK-N-DZ	BALB/c-nude小鼠	扩增	野生型	R110L	[24]

小鼠模型 Mouse model	优势 Advantage	局限性 Limitation	参考文献 Reference
Th-MYCN	代表高危NB型，成瘤率高	成瘤时间长，转移少	[39-40]
LSL-MYCN;dβh-iCre	比Th-MYCN更明确的转基因插入，发病率更高	转移率低	[31]
Th-MYCN/CASP8(KO)	存在转移，成瘤率高	引起原发肿瘤细胞外基质结构的改变	[41]
Th-MYCN/Trp53(KI)	诱导性P53丢失	P53突变多发于复发肿瘤中，小鼠的存活率低	[42]
ALK(F1174)	符合NB表型	临床常见率低	[33]
Th-MYCN/ALK(F1174)	成瘤率高，肿瘤生长快	相关性低	[35]
SV40 Tag	与NB表型一致，肿瘤发病率高，存在转移	所有小鼠在28周龄前死亡	[43]

小鼠模型 Mouse model	优势 Advantage	局限性 Limitation	参考文献 Reference
Th-MYCN	代表高危NB型，成瘤率高	成瘤时间长，转移少	[39-40]
LSL-MYCN;dβh-iCre	比Th-MYCN更明确的转基因插入，发病率更高	转移率低	[31]
Th-MYCN/CASP8(KO)	存在转移，成瘤率高	引起原发肿瘤细胞外基质结构的改变	[41]
Th-MYCN/Trp53(KI)	诱导性P53丢失	P53突变多发于复发肿瘤中，小鼠的存活率低	[42]
ALK(F1174)	符合NB表型	临床常见率低	[33]
Th-MYCN/ALK(F1174)	成瘤率高，肿瘤生长快	相关性低	[35]
SV40 Tag	与NB表型一致，肿瘤发病率高，存在转移	所有小鼠在28周龄前死亡	[43]

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神经母细胞瘤动物模型研究进展与应用

Advances and Applications in Animal Models of Neuroblastoma

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