Haploinsufficiency is not the key mechanism of pathogenesis in a heterozygous Elovl4 knockout mouse model of STGD3 disease.
Haploinsufficiency is not the key mechanism of pathogenesis in a heterozygous Elovl4 knockout mouse model of STGD3 disease.
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单倍体不足并不是 STGD3 疾病杂合 Elovl4 敲除小鼠模型发病机制的关键机制。
DOI：
10.1167/iovs.05-1527
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发表时间：
2006
影响因子：
4.4
通讯作者：
Sieving,PaulA
中科院分区：
文献类型：
--
作者：
Raz-Prag,Dorit;Ayyagari,Radha;Fariss,RobertN;Mandal,MdNawajesA;Vasireddy,Vidyullatha;Majchrzak,Sharon;Webber,AndreaL;Bush,RonaldA;SalemJr,Norman;Petrukhin,Konstantin;Sieving,PaulA
目的.常染色体显性遗传Stargardt样（STGD 3）疾病是由STGVL 4基因突变（极长链脂肪酸延长）引起的。本研究进行了表征的小鼠模型与有针对性的删除Elovl 4，并探讨该基因在视网膜/黄斑变性的作用。使用靶向Elov 14基因的外显子2的构建体来抑制基因的表达。Elov 14纯合幼仔不能存活，不能用于研究。因此，对16至22月龄的杂合Elovl 4 +/-小鼠和相同年龄的同窝野生型（WT）对照小鼠进行分析。表征包括检查基因信息和蛋白质水平，视网膜电图（ERG），视网膜形态和超微结构，以及血浆和视网膜脂肪酸组成。尽管Elovl 4 +/-视网膜中Elovl 4 mRNA的水平降低，但仅发现最小的形态学异常，并且与WT对照视网膜相比，Elovl 4 +/-视网膜中的视网膜（ERG）功能基本正常。Elovl 4 +/−小鼠的全身脂肪酸谱并不显著，尽管Elovl 4 +/−视网膜中几种脂肪酸的浓度显著较低，特别是单不饱和脂肪酸。该动物模型的详细表征提供了Elovl 4单倍不足不是STGD 3中潜在的关键疾病机制的第一个体内证据。结果与缺失突变的显性负性机制一致。Elovl 4基因敲除小鼠是有助于阐明疾病机制的三种互补动物模型之一。
purpose. Autosomal dominant Stargardt-like (STGD3) disease results from mutations in the ELOVL4 gene (elongation of very-long-chain fatty acids). This study was undertaken to characterize a mouse model with a targeted deletion of Elovl4 and to explore the role of this gene in retinal/macular degeneration.methods. A construct targeted to exon 2 of the Elovl4 gene was used to suppress expression of the gene. Elovl4 homozygous pups were nonviable and were not available for study. Hence, the analysis was performed on heterozygous Elovl4+/− mice 16 to 22 month of age and littermate wild-type (WT) control mice of the same age. Characterization included examining gene message and protein levels, electroretinogram (ERG), retinal morphology and ultrastructure, and plasma and retinal fatty acid composition.results. Although the level of Elovl4 mRNA was reduced in Elovl4+/− retinas, only minimal morphologic abnormalities were found, and the retinal (ERG) function was essentially normal in Elovl4+/− retinas compared with the WT control retinas. Systemic fatty acid profiles of Elovl4+/− mice were unremarkable, although the concentration of several fatty acids was significantly lower in Elovl4+/− retinas, particularly the monounsaturated fatty acids.conclusions. The detailed characterization of this animal model provides the first in vivo evidence that Elovl4 haploinsufficiency is not the underlying key disease mechanism in STGD3. The results are consistent with a dominant negative mechanism for the deletion mutation. The Elovl4 knockout mouse is one of three complementary animal models that will help elucidate the disease mechanism.
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DOI：
--
发表时间：
2000
期刊：
Investigative ophthalmology & visual science.
影响因子：
--
作者：
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通讯作者：
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作者：
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通讯作者：
LaVail, MM
影响因子：
6.5
作者：
W. R. Morrison;L. Smith
通讯作者：
W. R. Morrison;L. Smith
影响因子：
4.4
作者：
F. Delori;D. Goger;C. Dorey
通讯作者：
F. Delori;D. Goger;C. Dorey
视网膜中极长链（最多 36 个碳）四、五和六烯脂肪酸的合成。
DOI：
10.1042/bj2490191
发表时间：
1988
期刊：
The Biochemical journal
影响因子：
--
作者：
N. Rotstein;M. Aveldaño
通讯作者：
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