Essential role of Elovl4 in very long chain fatty acid synthesis, skin permeability barrier function, and neonatal survival.
Essential role of Elovl4 in very long chain fatty acid synthesis, skin permeability barrier function, and neonatal survival.
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DOI：
10.7150/ijbs.3.111
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发表时间：
2007-02-06
影响因子：
9.2
通讯作者：
Zhang K
中科院分区：
文献类型：
--
作者：
Cameron DJ;Tong Z;Yang Z;Kaminoh J;Kamiyah S;Chen H;Zeng J;Chen Y;Luo L;Zhang K
ELOVL4 基因突变已被证明会导致 Stargardt 样黄斑营养不良。 ELOVL4 是脂肪酸延伸酶家族的一部分，尚未指定其特定的延伸酶活性。我们生成了 Elovl4 Y270X 突变小鼠，并对纯合突变体和纯合 Elovl4 敲除小鼠进行了表征，以便更好地了解 Elovl4 的功能或作用。我们发现缺乏功能性 Elovl4 蛋白的小鼠会在围产期死亡。死亡原因似乎是由于皮肤渗透屏障形成缺陷导致脱水。进一步的生化分析表明，在纯合突变体和基因敲除小鼠皮肤中，长于 C26 的游离脂肪酸显着减少。这些结果表明这些长链脂肪酸在皮肤屏障发育中的重要性。此外，我们认为 Elovl4 可能参与 C26 和更长脂肪酸的延伸。
Mutations in the gene ELOVL4 have been shown to cause stargardt-like macular dystrophy. ELOVL4 is part of a family of fatty acid elongases and is yet to have a specific elongase activity assigned to it. We generated Elovl4 Y270X mutant mice and characterized the homozygous mutant as well as homozygous Elovl4 knockout mice in order to better understand the function or role of Elovl4. We found that mice lacking a functional Elovl4 protein died perinatally. The cause of death appears to be from dehydration due to faulty permeability barrier formation in the skin. Further biochemical analysis revealed a significant reduction in free fatty acids longer than C26 in homozygous mutant and knockout mouse skin. These results implicate the importance of these long chain fatty acids in skin barrier development. Furthermore, we suggest that Elovl4 is likely involved in the elongation of C26 and longer fatty acids.