Knockout of the folate transporter folt-1 causes germline and somatic defects in C. elegans.
Knockout of the folate transporter folt-1 causes germline and somatic defects in C. elegans.
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DOI：
10.1186/1471-213x-10-46
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发表时间：
2010-05-04
影响因子：
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通讯作者：
LaMunyon CW
中科院分区：
文献类型：
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作者：
Austin MU;Liau WS;Balamurugan K;Ashokkumar B;Said HM;LaMunyon CW
梭线虫基因FOLT-1是人还原叶酸载体基因的直系同源物。FOLT-1蛋白已被证明转运叶酸并参与蠕虫对外源叶酸的摄取。敲除突变的基因，folt-1（ok 1460），被证明会导致不育，在这里，我们调查不育的来源和体细胞功能的folt-1敲除的效果。我们的研究结果表明，folt-1（ok 1460）基因敲除的雌雄同体有一个显着减少的生殖细胞，产生少量的功能精子，只有很少产生一个功能卵母细胞。我们没有发现folt-1基因敲除突变体的生殖细胞凋亡增加的证据，这表明生殖细胞增殖是有缺陷的。虽然folt-1基因敲除的雄性是有生育能力的，但它们的精子发生率严重降低，而且这些雄性是非常差的母亲。这种交配缺陷可能是由于新陈代谢和/或其他躯体功能受损，因为folt-1基因敲除的雌雄同体显示出寿命缩短和排便间隔延长。FOLT-1蛋白功能影响索马和生殖细胞。FOLT-1（OK 1460）雌雄同体遭受严重缩短的寿命和导致不育的生殖系缺陷。与叶酸缺乏相关的生殖系缺陷在动物中广泛存在，在人类，小鼠，果蝇和这里，线虫中发现。
The C. elegans gene folt-1 is an ortholog of the human reduced folate carrier gene. The FOLT-1 protein has been shown to transport folate and to be involved in uptake of exogenous folate by worms. A knockout mutation of the gene, folt-1(ok1460), was shown to cause sterility, and here we investigate the source of the sterility and the effect of the folt-1 knockout on somatic function. Our results show that folt-1(ok1460) knockout hermaphrodites have a substantially reduced germline, generate a small number of functional sperm, and only rarely produce a functional oocyte. We found no evidence of increased apoptosis in the germline of folt-1 knockout mutants, suggesting that germline proliferation is defective. While folt-1 knockout males are fertile, their rate of spermatogenesis was severely diminished, and the males were very poor maters. The mating defect is likely due to compromised metabolism and/or other somatic functions, as folt-1 knockout hermaphrodites displayed a shortened lifespan and elongated defecation intervals. The FOLT-1 protein function affects both the soma and the germline. folt-1(ok1460) hermaphrodites suffer severely diminished lifespan and germline defects that result in sterility. Germline defects associated with folate deficiency appear widespread in animals, being found in humans, mice, fruit flies, and here, nematodes.