Elovl4 haploinsufficiency does not induce early onset retinal degeneration in mice.
Elovl4 haploinsufficiency does not induce early onset retinal degeneration in mice.
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Elovl4 单倍体不足不会诱导小鼠早发性视网膜变性。
DOI：
10.1016/j.visres.2006.10.023
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发表时间：
2007
期刊：
影响因子：
1.8
通讯作者：
Zhang,Kang
中科院分区：
文献类型：
--
作者：
Li,Wenmei;Chen,Yali;Cameron,DJoshua;Wang,Changguan;Karan,Goutam;Yang,Zhenglin;Zhao,Yu;Pearson,Erik;Chen,Haoyu;Deng,Chuxia;Howes,Kimberly;Zhang,Kang
ELOVL4最早被发现是Stargardt黄斑营养不良（STGD3, MIM 600110）的致病基因。迄今为止，已经确定了三种ELOVL4突变，所有这些突变都导致蛋白截短，从而诱导常染色体显性的青少年黄斑变性。基于序列同源性，ELOVL4被认为是长链脂肪酸延伸蛋白家族中的另一个成员。然而，ELOVL4的正常功能尚不清楚。我们产生了Elovl4基因敲除小鼠，以确定Elovl4基因缺失是否会影响视网膜发育或功能。在这里，我们发现Elovl4基因敲除小鼠，虽然围产期死亡，但在出生当天死亡前表现出正常的视网膜发育。此外，Elovl4杂合小鼠的出生后视网膜发育正常。因此，常染色体显性黄斑变性中野生型ELOVL4的单倍性不足可能不会导致STGD3患者的幼年黄斑变性。然而，我们发现，相对于野生型Elovl4+/+小鼠，Elovl4+/+小鼠表现出增强的ERG暗位和光位a和b波，这表明Elovl4水平的降低可能会影响视网膜电生理反应。
ELOVL4 was first identified as a disease-causing gene in Stargardt macular dystrophy (STGD3, MIM 600110.) To date, three ELOVL4 mutations have been identified, all of which result in truncated proteins which induce autosomal dominant juvenile macular degenerations. Based on sequence homology, ELOVL4 is thought to be another member within a family of proteins functioning in the elongation of long chain fatty acids. However, the normal function of ELOVL4 is unclear. We generated Elovl4 knockout mice to determine if Elovl4 loss affects retinal development or function. Here we show that Elovl4 knockout mice, while perinatal lethal, exhibit normal retinal development prior to death at day of birth. Further, postnatal retinal development in Elovl4 heterozygous mice appears normal. Therefore haploinsufficiency for wildtype ELOVL4 in autosomal dominant macular degeneration likely does not contribute to juvenile macular degeneration in STGD3 patients. We found, however, that Elovl4+/−mice exhibit enhanced ERG scotopic and photopic a and b waves relative to wildtype Elovl4+/+mice suggesting that reduced Elovl4 levels may impact retinal electrophysiological responses.