Mutant SOD1 knockdown in all cell types ameliorates disease in G85R SOD1 mice with a limited additional effect over knockdown restricted to motor neurons.
Mutant SOD1 knockdown in all cell types ameliorates disease in G85R SOD1 mice with a limited additional effect over knockdown restricted to motor neurons.
复制标题
所有细胞类型中的突变 SOD1 敲除均可改善 G85R SOD1 小鼠的疾病，但与仅限于运动神经元的敲除相比，附加效果有限。
DOI：
10.1111/j.1471-4159.2010.06594.x
复制
发表时间：
2010
影响因子：
4.7
通讯作者：
Roos,RaymondP
中科院分区：
文献类型：
--
作者：
Wang,Lijun;Grisotti,Gabriella;Roos,RaymondP
J. Neurochem.(2010) 10.1111/j.1471‐4159.2010.06594.xAbstractApproximately 10% of patients with amyotrophic lateral sclerosis (ALS) have familial ALS (FALS), and 20% of FALS is caused by mutant Cu/Zn superoxide dismutase type 1 (MTSOD1). Previous studies have convincingly demonstrated that MTSOD1 expression in other cell types besides motor neurons (MNs) contributes to disease in MTSOD1 FALS transgenic mice. Using Cre/LoxP methods, we knocked down G85R SOD1 mRNA by 66% in all cell types in 3‐month‐old FALS transgenic mice, delaying disease onset and lengthening disease duration. Surprisingly, the effect on onset and early disease duration was similar to that seen in FALS transgenic mice with ∼25% knockdown prenatally in G85R SOD1 mRNA restricted to MNs and some interneurons. These results demonstrate no clear cumulative effect on disease onset or early disease duration from knocking down G85R SOD1 in other cell types in addition to MNs/interneurons; the findings bring up the possibility that MTSOD1 has a pathogenic effect early in life that our later knockdown did not affect. Despite the more limited amelioration of disease than expected, the effect of the knockdown on disease supports the value of this approach in FALS patients and asymptomatic individuals with SOD1 mutations.
