肌萎缩侧索硬化症小鼠模型研究进展

罗莲莲, 袁艳春, 王俊岭, 时广森

Advances in Mouse Models of Amyotrophic Lateral Sclerosis

LUO Lianlian, YUAN Yanchun, WANG Junling, SHI Guangsen

表1 常用的肌萎缩侧索硬化症小鼠模型及其表型特征

Table 1 Commonly used mouse models of amyotrophic lateral sclerosis and their phenotypic characteristics

肌萎缩侧索硬化症小鼠模型 ALS mouse model	基因 Gene	氨基酸改变 Amino acid substitution	机制 Mechanism	瘫痪 Paralysis	认知异常 Cognitive impairment	神经元丢失 Neuron loss	神经胶质增生 Gliosis	胞质包涵体 Cytoplasmic inclusion bodies	参考文献 References
转基因小鼠模型 Transgenic mouse model	hSOD1	WT	-	√	-	√	√	SOD1, VAC	[81]
	hSOD1	D90A	-	-	-	√	√	SOD1, VAC	[82]
	hSOD1	G93A	GOF	-	√	√	-	-	[83]
	hTDP-43	WT	-	√	-	√	√	TDP-43, UBI	[32]
	TDP-43	A315T	GOF	-	√	-	√	TDP-43, UBI	[34]
	hTDP-43	Q331K	LOF/GOF	-	-	√	√	×	[31]
	hTDP-43	M337V	GOF	-	-	√	√	×	[31]
	hFUS	WT	GOF	-	√	×	×	×	[84]
	hFUS	R521C	GOF	-	√	-	√	×	[84]
	hFUS	R521C	GOF	√	-	√	√	×	[38]
	hFUS	ΔNLS	GOF	√	-	√	√	FUS	[40]
	hC9orf72	[500] n	GOF	√	√	√	√	DPR, RNA foci, TDP-43	[47]
	hC9orf72	[500] n	-	-	√	×	√	DPR, RNA foci	[85]
	hC9orf72	[500] n	-	-	-	√	√	RNA foci	[48]
基因敲入小鼠模型 Knock-in mouse model	TDP-43	N390D	GOF	-	-	√	√	TDP-43	[57]
	TDP-43	Q331K	GOF	×	√	√	-	×	[55]
	FUS	P517L	GOF	-	-	√	√	FUS	[86]
	FUS	Δ14	GOF	-	-	√	√	FUS	[86]
	FUS	ΔNLS	-	-	-	√	-	FUS	[87]
	C9orf72	(GR)400或(PR)400	-	-	-	√	×	DPR	[88]
	CLCC1	K298A	LOF	-	-	√	-	TDP-43, UBI	[52]
	PCDHA9	L700P	-	√	-	√	√	TDP-43	[53]
腺相关病毒过表达小鼠模型 Adeno-associated virus-mediated overexpression mouse model	TDP-43	WT	-	√	-	√	-	-	[76]
	TDP-43	M337V	GOF	√	-	√	√	TDP-43	[75]
	C9orf72	[66] n	GOF	√	√	√	√	DPR, RNA foci, TDP-43	[71]
	C9orf72	[149] n	GOF	√	√	√	√	DPR, RNA foci, TDP-43	[71]
	C9orf72	[100] n	LOF	×	√	√	√	TDP-43	[89]
	SARM1	V184G	-	√	-	-	-	-	[78]